Presentación para el simposio satélite de Amarey en el marco del congreso de los 85 años del Instituto Nacional de Cancerología, Hotel Hyatt, 29.08.2019, Bogotá
This document summarizes treatment approaches for triple negative breast cancer (TNBC), including neoadjuvant and adjuvant therapies. It discusses how TNBC is an aggressive disease that is often chemotherapy responsive initially but develops resistance rapidly. Neoadjuvant platinum chemotherapy is shown to increase pathologic complete response rates compared to standard regimens. Ongoing research is exploring eliminating anthracyclines and combining immunotherapy with chemotherapy to further improve outcomes for patients with early and advanced TNBC. Large phase III trials are currently investigating the addition of checkpoint inhibitors like pembrolizumab to neoadjuvant regimens.
The Trial Assigning IndividuaLized Options for Treatment (Rx) -TAILORx,TAILORx clinical trial showed that most women with hormone receptor (HR)–positive, HER2-negative, axillary node–negative early-stage breast cancer and a mid-range score on a 21-tumor gene expression assay (Oncotype DX® Breast Recurrence Score) do not need chemotherapy after surgery
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
The document discusses adjuvant therapy for renal cell carcinoma. It reviews several studies that evaluated cytokines like interferon-alpha and interleukin-2 alone or in combination as adjuvant therapy after nephrectomy. The studies found no overall survival or disease-free survival benefits for cytokines in non-metastatic renal cell carcinoma patients treated with nephrectomy. More recent studies evaluated tyrosine kinase inhibitors like sunitinib, sorafenib, and pazopanib as adjuvant therapy and found improvements in disease-free survival and overall survival compared to placebo for high-risk patients after nephrectomy. The document provides guidelines on identifying candidates for adjuvant sunitinib therapy and reviews dosing, administration, and adverse effects
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
This study evaluated the roles of adjuvant chemoradiotherapy and chemotherapy in patients with resected pancreatic cancer. 541 patients were randomized to one of four groups: chemoradiotherapy, chemotherapy, both, or observation. The results showed no survival benefit for adjuvant chemoradiotherapy, with a median survival of 15.5 months compared to 16.1 months without chemoradiotherapy. However, there was evidence of a survival benefit for adjuvant chemotherapy, with a median survival of 19.7 months compared to 14 months without chemotherapy. This study provided evidence that adjuvant chemotherapy may improve survival for patients with resected pancreatic cancer, but did not show a benefit for chemoradiotherapy.
Strategies for Managing Recurrent Ovarian Cancerbkling
When ovarian cancer returns, it's not uncommon to experience a range of emotions and feel overwhelmed. But it's important to remember that recurrent ovarian cancer can often be successfully treated. Dr. Shannon N. Westin, gynecologic oncologist and clinical investigator at MD Anderson Cancer Center, goes over the latest treatment options for recurrent disease.
This document summarizes treatment approaches for triple negative breast cancer (TNBC), including neoadjuvant and adjuvant therapies. It discusses how TNBC is an aggressive disease that is often chemotherapy responsive initially but develops resistance rapidly. Neoadjuvant platinum chemotherapy is shown to increase pathologic complete response rates compared to standard regimens. Ongoing research is exploring eliminating anthracyclines and combining immunotherapy with chemotherapy to further improve outcomes for patients with early and advanced TNBC. Large phase III trials are currently investigating the addition of checkpoint inhibitors like pembrolizumab to neoadjuvant regimens.
The Trial Assigning IndividuaLized Options for Treatment (Rx) -TAILORx,TAILORx clinical trial showed that most women with hormone receptor (HR)–positive, HER2-negative, axillary node–negative early-stage breast cancer and a mid-range score on a 21-tumor gene expression assay (Oncotype DX® Breast Recurrence Score) do not need chemotherapy after surgery
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
The document discusses adjuvant therapy for renal cell carcinoma. It reviews several studies that evaluated cytokines like interferon-alpha and interleukin-2 alone or in combination as adjuvant therapy after nephrectomy. The studies found no overall survival or disease-free survival benefits for cytokines in non-metastatic renal cell carcinoma patients treated with nephrectomy. More recent studies evaluated tyrosine kinase inhibitors like sunitinib, sorafenib, and pazopanib as adjuvant therapy and found improvements in disease-free survival and overall survival compared to placebo for high-risk patients after nephrectomy. The document provides guidelines on identifying candidates for adjuvant sunitinib therapy and reviews dosing, administration, and adverse effects
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
This study evaluated the roles of adjuvant chemoradiotherapy and chemotherapy in patients with resected pancreatic cancer. 541 patients were randomized to one of four groups: chemoradiotherapy, chemotherapy, both, or observation. The results showed no survival benefit for adjuvant chemoradiotherapy, with a median survival of 15.5 months compared to 16.1 months without chemoradiotherapy. However, there was evidence of a survival benefit for adjuvant chemotherapy, with a median survival of 19.7 months compared to 14 months without chemotherapy. This study provided evidence that adjuvant chemotherapy may improve survival for patients with resected pancreatic cancer, but did not show a benefit for chemoradiotherapy.
Strategies for Managing Recurrent Ovarian Cancerbkling
When ovarian cancer returns, it's not uncommon to experience a range of emotions and feel overwhelmed. But it's important to remember that recurrent ovarian cancer can often be successfully treated. Dr. Shannon N. Westin, gynecologic oncologist and clinical investigator at MD Anderson Cancer Center, goes over the latest treatment options for recurrent disease.
Report Back from SGO: What's the Latest in Ovarian Cancer?bkling
Dr. Joyce F. Liu, Director of Clinical Research for Gynecologic Oncology at Dana-Farber Cancer Institute, provides a comprehensive update from the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.
The document summarizes information about pertuzumab for the treatment of HER2-positive breast cancer. It discusses pertuzumab's mechanism of action in blocking HER2 dimerization and signaling pathways. Clinical studies show pertuzumab improves pathological complete response rates when added to neoadjuvant or adjuvant trastuzumab-containing regimens. The APHINITY study demonstrated pertuzumab extended invasive disease-free survival compared to placebo when given adjuvantly for 1 year. Pertuzumab is generally well-tolerated with low risks of cardiac toxicity when combined with trastuzumab.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
Advances in management of castration resistant prostate cancerAlok Gupta
Given this patient's advanced age and comorbidities, I would recommend abiraterone acetate as the second line treatment option post enzalutamide progression. Abiraterone has shown survival benefit with good tolerability in older patients with comorbidities in the COU-AA-301 trial. Cabazitaxel could be considered but may have higher toxicity risks in this patient. Close monitoring would be needed.
Immunotherapy maintenence for advanced urothelial cancerChandan K Das
- JAVELIN Bladder 100 was a phase 3 trial investigating avelumab maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial carcinoma.
- The trial found avelumab maintenance significantly improved overall survival compared to best supportive care alone, with a 31% reduction in risk of death. Progression-free survival was also significantly improved.
- Subgroup analyses found overall survival benefits were consistent across all patient subgroups, including those with PD-L1-negative tumors. Response rates were also higher with avelumab maintenance.
- The safety profile of avelumab was manageable, with most treatment-related adverse events being grade 1-2 in severity and no new safety signals
1) The AURELIA trial evaluated bevacizumab combined with chemotherapy versus chemotherapy alone for platinum-resistant recurrent ovarian cancer.
2) The trial found that progression-free survival was significantly longer in the bevacizumab combination group compared to the chemotherapy alone group (median 6.7 months vs 3.4 months).
3) Rates of objective response were also significantly higher in the bevacizumab combination group compared to chemotherapy alone (30.9% vs 12.6%).
This document summarizes the treatment landscape for ovarian cancer. It discusses standard first-line treatment options including platinum-based chemotherapy with carboplatin and paclitaxel, as well as the importance of adequate surgery to remove as much of the tumor as possible. It also reviews several phase 3 clinical trials investigating the addition of angiogenesis inhibitors like bevacizumab to chemotherapy regimens. Trials like ICON7 and GOG 218 found improved progression-free survival when bevacizumab was added to first-line treatment. For recurrent disease, bevacizumab was also found to improve outcomes when added to chemotherapy in platinum-sensitive patients based on studies like OCEANS and GOG-213. Residual
Update on Management of Triple Negative Breast Cancerspa718
This document provides an update on the management of triple negative breast cancer from Dr. Banu Arun at MD Anderson Cancer Center. It discusses that triple negative breast cancer is a heterogeneous disease comprised of several molecular subtypes with different characteristics and potential treatment targets. Clinical trials exploring chemotherapy regimens, platinum agents, PARP inhibitors, anti-angiogenic drugs, and immunotherapies are summarized. Ongoing research aims to better define the subtypes in order to personalize treatment for triple negative breast cancer patients.
Sequencing therapy for crcp a practical approachMohamed Abdulla
This document discusses sequencing therapy for castration-resistant prostate cancer (CRPC). It provides an overview of prostate cancer as an androgenic disease and summarizes several key clinical trials investigating the efficacy of abiraterone and enzalutamide in both pre-docetaxel and post-docetaxel CRPC patients. It concludes by presenting NCCN guidelines for sequencing CRPC therapies based on disease stage and symptoms.
The document discusses neoadjuvant and adjuvant therapies for HER2-positive breast cancer. It summarizes several clinical trials evaluating combinations of trastuzumab, pertuzumab, docetaxel, and other chemotherapies in the neoadjuvant and adjuvant settings. Combinations including dual HER2 blockade with trastuzumab and pertuzumab were found to significantly improve pathological complete response rates compared to other regimens. Ongoing studies continue exploring new targeted agents and combinations to further improve outcomes for patients with high-risk HER2-positive breast cancer.
Adjuvant Endocrine Therapy For Postmenopausal Breast CancerEmad Shash
Questions Covered in the presentation:
• Should patients receive an AI or Tamoxifen?
• Should patients receive monotherapy (AI or Tamoxifen alone) or sequential
therapy using both?
• 5 vs 10 years of therapy?
• If More than 5 years of endocrine therapy, which class to be used
This downloadable slidedeck, presented in a regional grand rounds series, focuses on increasing awareness about current and emerging treatment options for patients with newly diagnosed and recurrent ovarian cancer.
This phase 3 trial investigated adding abemaciclib to standard adjuvant endocrine therapy in patients with hormone receptor-positive, HER2-negative, lymph node-positive, high-risk early breast cancer. At the interim analysis, the addition of abemaciclib resulted in a statistically significant improvement in invasive disease-free survival compared to endocrine therapy alone. The most common adverse events with abemaciclib were diarrhea, neutropenia, and fatigue. Additional follow-up is still needed to determine if the benefit persists for later recurrences and overall survival.
1) Hormonal therapy targets estrogen receptor positive breast cancers, which comprise around 70% of cases. It works by blocking the effects of estrogen through various mechanisms.
2) Available hormonal therapies include selective estrogen receptor modulators (SERMs) like tamoxifen, aromatase inhibitors, LHRH analogues, and ovarian ablation through surgery or radiation.
3) In the adjuvant setting, 5 years of tamoxifen reduces recurrence and mortality rates in both pre- and postmenopausal women. Longer durations up to 10 years provide further benefits in high risk patients. Aromatase inhibitors are now preferred over tamoxifen for initial therapy in postmenopausal women.
Presented by the Johns Hopkins University School of Medicine and
produced in collaboration with the Institute for Medical Education & Research (IMER).
Review a downloadable slide deck by, covering the most clinically relevant new data reported from Expert Video Viewpoints on Castration-Resistant Prostate Cancer: Care Across the Continuum by:
Emmanuel Antonarakis, MBBCh
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Leonard G. Gomella, MD, FACS
Thomas Jefferson University
Jefferson Kimmel Cancer Center
A. Oliver Sartor, MD
Tulane University School of Medicine
Target Audience
Medical oncologists, urologists, radiation oncologists, and other healthcare professionals involved in the treatment of patients with castration-resistant prostate cancer (CRPC). There are no prerequisites.
Activity Overview
In this video, a panel of expert thought leaders will discuss the optimal management and emerging agents across the CRPC treatment continuum. Topics will include identification and initial treatment of CRPC, metastatic CRPC progression, future novel treatment for CRPC patients, and expert perspectives on case examples to decipher optimal treatment of CRPC.
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of December 2011. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
The Changing Role of PARP Inhibitors in the Treatment of Ovarian Cancerbkling
In recent years, researchers have been looking into using a class of drugs called PARP inhibitors to prevent the progression and recurrence of ovarian cancer. Dr. Kathleen Moore of Stephenson Cancer Center, Principal Investigator of the SOLO-1 trial, explains how the results of this trial may affect ovarian cancer patients and where research on ovarian cancer treatment is headed next.
This phase 3 randomized trial investigated the incorporation of bevacizumab and nonplatinum combination chemotherapy in the treatment of advanced cervical cancer. It found that the addition of bevacizumab to chemotherapy significantly improved median overall survival compared to chemotherapy alone, from 13.3 months to 16.8 months. Bevacizumab also significantly improved progression-free survival and response rates. The benefit was observed across patient subgroups and did not negatively impact quality of life. Higher rates of gastrointestinal fistulas and thromboembolic events occurred with bevacizumab. The trial demonstrated that bevacizumab provided meaningful clinical benefit when added to chemotherapy for advanced cervical cancer.
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Olaparib is an oral PARP inhibitor that has shown efficacy in the treatment of breast and ovarian cancers associated with BRCA mutations. In breast cancer, phase III trials OlympiA and OlympiAD demonstrated that olaparib improves invasive disease-free survival and progression-free survival, respectively, in patients with germline BRCA mutations. In ovarian cancer, phase III trials SOLO-1, PAOLA-1, and PRIMA found that olaparib improves progression-free survival when used as maintenance therapy or in combination with chemotherapy in patients with BRCA mutations. Olaparib is now approved for several indications based on these trials and provides an important targeted treatment option for cancers associated
Breast cancer oncotype-dx.. by dr.Kamel Farag, MDKamelFarag4
This document discusses factors oncologists consider when determining if a patient with hormone receptor-positive breast cancer can skip chemotherapy.
It begins by explaining the three main breast cancer subtypes and that chemotherapy is usually only necessary for triple-negative and HER2-positive cancers. For hormone receptor-positive cancers, chemotherapy may have a lesser role since patients benefit greatly from anti-estrogen medications.
It then discusses tools oncologists use to assess risk, such as genomic tests like Oncotype DX that provide recurrence scores, and clinicopathologic factors like tumor grade and size. Large clinical trials like TAILORx and RxPONDER helped establish cut-offs for recurrence scores below which chemotherapy provided little additional benefit
The document discusses the use of genomics in early stage breast cancer treatment. It describes how genomics can provide personalized treatment by understanding each tumor's biology and risk of recurrence. Two multi-gene assays, Mammaprint and Oncotype DX, are discussed. Oncotype DX has been clinically validated to predict recurrence risk and chemotherapy benefit in node-negative patients. Studies also show it can predict outcomes for node-positive patients treated with tamoxifen. The results from these assays often change treatment decisions by identifying patients unlikely to benefit from chemotherapy.
Report Back from SGO: What's the Latest in Ovarian Cancer?bkling
Dr. Joyce F. Liu, Director of Clinical Research for Gynecologic Oncology at Dana-Farber Cancer Institute, provides a comprehensive update from the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.
The document summarizes information about pertuzumab for the treatment of HER2-positive breast cancer. It discusses pertuzumab's mechanism of action in blocking HER2 dimerization and signaling pathways. Clinical studies show pertuzumab improves pathological complete response rates when added to neoadjuvant or adjuvant trastuzumab-containing regimens. The APHINITY study demonstrated pertuzumab extended invasive disease-free survival compared to placebo when given adjuvantly for 1 year. Pertuzumab is generally well-tolerated with low risks of cardiac toxicity when combined with trastuzumab.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
Advances in management of castration resistant prostate cancerAlok Gupta
Given this patient's advanced age and comorbidities, I would recommend abiraterone acetate as the second line treatment option post enzalutamide progression. Abiraterone has shown survival benefit with good tolerability in older patients with comorbidities in the COU-AA-301 trial. Cabazitaxel could be considered but may have higher toxicity risks in this patient. Close monitoring would be needed.
Immunotherapy maintenence for advanced urothelial cancerChandan K Das
- JAVELIN Bladder 100 was a phase 3 trial investigating avelumab maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial carcinoma.
- The trial found avelumab maintenance significantly improved overall survival compared to best supportive care alone, with a 31% reduction in risk of death. Progression-free survival was also significantly improved.
- Subgroup analyses found overall survival benefits were consistent across all patient subgroups, including those with PD-L1-negative tumors. Response rates were also higher with avelumab maintenance.
- The safety profile of avelumab was manageable, with most treatment-related adverse events being grade 1-2 in severity and no new safety signals
1) The AURELIA trial evaluated bevacizumab combined with chemotherapy versus chemotherapy alone for platinum-resistant recurrent ovarian cancer.
2) The trial found that progression-free survival was significantly longer in the bevacizumab combination group compared to the chemotherapy alone group (median 6.7 months vs 3.4 months).
3) Rates of objective response were also significantly higher in the bevacizumab combination group compared to chemotherapy alone (30.9% vs 12.6%).
This document summarizes the treatment landscape for ovarian cancer. It discusses standard first-line treatment options including platinum-based chemotherapy with carboplatin and paclitaxel, as well as the importance of adequate surgery to remove as much of the tumor as possible. It also reviews several phase 3 clinical trials investigating the addition of angiogenesis inhibitors like bevacizumab to chemotherapy regimens. Trials like ICON7 and GOG 218 found improved progression-free survival when bevacizumab was added to first-line treatment. For recurrent disease, bevacizumab was also found to improve outcomes when added to chemotherapy in platinum-sensitive patients based on studies like OCEANS and GOG-213. Residual
Update on Management of Triple Negative Breast Cancerspa718
This document provides an update on the management of triple negative breast cancer from Dr. Banu Arun at MD Anderson Cancer Center. It discusses that triple negative breast cancer is a heterogeneous disease comprised of several molecular subtypes with different characteristics and potential treatment targets. Clinical trials exploring chemotherapy regimens, platinum agents, PARP inhibitors, anti-angiogenic drugs, and immunotherapies are summarized. Ongoing research aims to better define the subtypes in order to personalize treatment for triple negative breast cancer patients.
Sequencing therapy for crcp a practical approachMohamed Abdulla
This document discusses sequencing therapy for castration-resistant prostate cancer (CRPC). It provides an overview of prostate cancer as an androgenic disease and summarizes several key clinical trials investigating the efficacy of abiraterone and enzalutamide in both pre-docetaxel and post-docetaxel CRPC patients. It concludes by presenting NCCN guidelines for sequencing CRPC therapies based on disease stage and symptoms.
The document discusses neoadjuvant and adjuvant therapies for HER2-positive breast cancer. It summarizes several clinical trials evaluating combinations of trastuzumab, pertuzumab, docetaxel, and other chemotherapies in the neoadjuvant and adjuvant settings. Combinations including dual HER2 blockade with trastuzumab and pertuzumab were found to significantly improve pathological complete response rates compared to other regimens. Ongoing studies continue exploring new targeted agents and combinations to further improve outcomes for patients with high-risk HER2-positive breast cancer.
Adjuvant Endocrine Therapy For Postmenopausal Breast CancerEmad Shash
Questions Covered in the presentation:
• Should patients receive an AI or Tamoxifen?
• Should patients receive monotherapy (AI or Tamoxifen alone) or sequential
therapy using both?
• 5 vs 10 years of therapy?
• If More than 5 years of endocrine therapy, which class to be used
This downloadable slidedeck, presented in a regional grand rounds series, focuses on increasing awareness about current and emerging treatment options for patients with newly diagnosed and recurrent ovarian cancer.
This phase 3 trial investigated adding abemaciclib to standard adjuvant endocrine therapy in patients with hormone receptor-positive, HER2-negative, lymph node-positive, high-risk early breast cancer. At the interim analysis, the addition of abemaciclib resulted in a statistically significant improvement in invasive disease-free survival compared to endocrine therapy alone. The most common adverse events with abemaciclib were diarrhea, neutropenia, and fatigue. Additional follow-up is still needed to determine if the benefit persists for later recurrences and overall survival.
1) Hormonal therapy targets estrogen receptor positive breast cancers, which comprise around 70% of cases. It works by blocking the effects of estrogen through various mechanisms.
2) Available hormonal therapies include selective estrogen receptor modulators (SERMs) like tamoxifen, aromatase inhibitors, LHRH analogues, and ovarian ablation through surgery or radiation.
3) In the adjuvant setting, 5 years of tamoxifen reduces recurrence and mortality rates in both pre- and postmenopausal women. Longer durations up to 10 years provide further benefits in high risk patients. Aromatase inhibitors are now preferred over tamoxifen for initial therapy in postmenopausal women.
Presented by the Johns Hopkins University School of Medicine and
produced in collaboration with the Institute for Medical Education & Research (IMER).
Review a downloadable slide deck by, covering the most clinically relevant new data reported from Expert Video Viewpoints on Castration-Resistant Prostate Cancer: Care Across the Continuum by:
Emmanuel Antonarakis, MBBCh
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Leonard G. Gomella, MD, FACS
Thomas Jefferson University
Jefferson Kimmel Cancer Center
A. Oliver Sartor, MD
Tulane University School of Medicine
Target Audience
Medical oncologists, urologists, radiation oncologists, and other healthcare professionals involved in the treatment of patients with castration-resistant prostate cancer (CRPC). There are no prerequisites.
Activity Overview
In this video, a panel of expert thought leaders will discuss the optimal management and emerging agents across the CRPC treatment continuum. Topics will include identification and initial treatment of CRPC, metastatic CRPC progression, future novel treatment for CRPC patients, and expert perspectives on case examples to decipher optimal treatment of CRPC.
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of December 2011. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
The Changing Role of PARP Inhibitors in the Treatment of Ovarian Cancerbkling
In recent years, researchers have been looking into using a class of drugs called PARP inhibitors to prevent the progression and recurrence of ovarian cancer. Dr. Kathleen Moore of Stephenson Cancer Center, Principal Investigator of the SOLO-1 trial, explains how the results of this trial may affect ovarian cancer patients and where research on ovarian cancer treatment is headed next.
This phase 3 randomized trial investigated the incorporation of bevacizumab and nonplatinum combination chemotherapy in the treatment of advanced cervical cancer. It found that the addition of bevacizumab to chemotherapy significantly improved median overall survival compared to chemotherapy alone, from 13.3 months to 16.8 months. Bevacizumab also significantly improved progression-free survival and response rates. The benefit was observed across patient subgroups and did not negatively impact quality of life. Higher rates of gastrointestinal fistulas and thromboembolic events occurred with bevacizumab. The trial demonstrated that bevacizumab provided meaningful clinical benefit when added to chemotherapy for advanced cervical cancer.
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Olaparib is an oral PARP inhibitor that has shown efficacy in the treatment of breast and ovarian cancers associated with BRCA mutations. In breast cancer, phase III trials OlympiA and OlympiAD demonstrated that olaparib improves invasive disease-free survival and progression-free survival, respectively, in patients with germline BRCA mutations. In ovarian cancer, phase III trials SOLO-1, PAOLA-1, and PRIMA found that olaparib improves progression-free survival when used as maintenance therapy or in combination with chemotherapy in patients with BRCA mutations. Olaparib is now approved for several indications based on these trials and provides an important targeted treatment option for cancers associated
Breast cancer oncotype-dx.. by dr.Kamel Farag, MDKamelFarag4
This document discusses factors oncologists consider when determining if a patient with hormone receptor-positive breast cancer can skip chemotherapy.
It begins by explaining the three main breast cancer subtypes and that chemotherapy is usually only necessary for triple-negative and HER2-positive cancers. For hormone receptor-positive cancers, chemotherapy may have a lesser role since patients benefit greatly from anti-estrogen medications.
It then discusses tools oncologists use to assess risk, such as genomic tests like Oncotype DX that provide recurrence scores, and clinicopathologic factors like tumor grade and size. Large clinical trials like TAILORx and RxPONDER helped establish cut-offs for recurrence scores below which chemotherapy provided little additional benefit
The document discusses the use of genomics in early stage breast cancer treatment. It describes how genomics can provide personalized treatment by understanding each tumor's biology and risk of recurrence. Two multi-gene assays, Mammaprint and Oncotype DX, are discussed. Oncotype DX has been clinically validated to predict recurrence risk and chemotherapy benefit in node-negative patients. Studies also show it can predict outcomes for node-positive patients treated with tamoxifen. The results from these assays often change treatment decisions by identifying patients unlikely to benefit from chemotherapy.
1) The Spanish GEICAM study found that after using the Oncotype DX test, the treatment recommendation changed in 31.8% of early-stage breast cancer patients, with the most common change being a switch from chemotherapy plus hormone therapy to hormone therapy alone (20.6% of cases).
2) Factors like higher tumor grade, high Ki-67, and positive progesterone receptor status were associated with an increased likelihood of changing the treatment recommendation.
3) Medical oncologists reported increased confidence in their treatment recommendations after receiving the Oncotype DX results.
The document discusses several gene expression profiling tests for early breast cancer, including OncotypeDX, MammaPrint, and TAILORx. OncotypeDX analyzes the expression of 21 genes to calculate a recurrence score that predicts the likelihood of distant recurrence within 10 years for tamoxifen-treated patients. MammaPrint analyzes 70 genes to classify patients into low or high risk groups. The TAILORx clinical trial aims to determine which patients with early breast cancer and OncotypeDX scores of 11-25 benefit from chemotherapy using a randomized design.
1) Adjuvant chemotherapy reduces breast cancer mortality by 17-33% according to meta-analyses, with anthracycline-based regimens being more effective than CMF.
2) For HER2-positive early breast cancer, adjuvant chemotherapy plus trastuzumab is the standard of care, improving disease-free and overall survival compared to chemotherapy alone.
3) For endocrine-responsive early breast cancer, the absolute benefit of chemotherapy depends on risk factors; genomic signatures can help identify patients most likely to benefit from chemotherapy in addition to endocrine therapy.
1) Adjuvant chemotherapy reduces breast cancer mortality by 17-33% according to meta-analyses, with anthracycline-based regimens being more effective than CMF.
2) For HER2-positive early breast cancer, adjuvant chemotherapy plus trastuzumab is the standard of care, improving disease-free and overall survival compared to chemotherapy alone.
3) For endocrine-responsive early breast cancer, the absolute benefit of chemotherapy depends on risk factors; genomic signatures can help identify patients most likely to benefit from chemotherapy in addition to endocrine therapy.
1) A study analyzed data from 687 patients with triple negative breast cancer who received surgery and adjuvant chemotherapy. The study found that as the time between surgery and starting chemotherapy increased, both 10-year disease-free survival and 10-year overall survival decreased.
2) Patients who started chemotherapy within 30 days of surgery had the best outcomes, with 10-year disease-free survival of 81.4% and 10-year overall survival of 82%.
3) Delaying the start of adjuvant chemotherapy by more than 90 days after surgery was associated with significantly worse survival outcomes.
1. Adjuvant therapies like tamoxifen and chemotherapy have been shown to decrease the risk of recurrence and mortality from early breast cancer based on large meta-analyses.
2. Molecular classification of early breast cancer into subgroups like luminal A, luminal B, HER2-positive, and triple-negative helps determine which patients are likely to benefit most from adjuvant chemotherapy, hormonal therapy, or targeted therapies.
3. Large randomized controlled trials have demonstrated improved outcomes with anthracycline-based chemotherapy compared to CMF and the addition of taxanes to anthracycline regimens compared to anthracyclines alone in the adjuvant setting.
This document discusses stereotactic body radiation therapy (SBRT) for head and neck cancers. It provides an overview of SBRT indications, efficacy, toxicity profiles, quality of life outcomes, fractionation schedules, target definition, constraints, and the role of cetuximab. Several studies on SBRT for recurrent head and neck cancers, primary cancers metastatic to the head and neck region, and target volume delineation are summarized. Toxicities are generally low but carotid blowout syndrome remains a concern, especially for tumors adjacent to carotid arteries.
Frédérique Penault Llorca : Oncotype DX® Breast Cancer Assay: Results and Im...breastcancerupdatecongress
This document summarizes several landmark studies that have validated the clinical utility of the Oncotype DX Breast Cancer Assay. It describes how the assay analyzes the expression of 21 genes linked to breast cancer recurrence and predicts 10-year recurrence risk and likelihood of chemotherapy benefit. Multiple large randomized controlled trials are cited that demonstrate the assay's ability to accurately prognose recurrence risk and predict response to tamoxifen versus tamoxifen plus chemotherapy based on a patient's Recurrence Score result. The assay has shown consistent results across diverse patient populations and treatment settings.
EBRT in breast cancer: Evolution to cutting edgePramod Tike
EBRT in breast cancer has evolved significantly over time. Randomized controlled trials have shown that post-operative radiotherapy after breast-conserving surgery reduces local recurrence rates compared to surgery alone. Hypofractionated radiotherapy regimens have been shown to be as effective as conventional fractionation with reduced toxicity. Newer radiotherapy techniques such as forward-planned intensity-modulated radiation therapy (IMRT) allow improved dose distribution and reduced normal tissue exposure. Partial breast irradiation is being investigated as an alternative to whole breast irradiation for selected low-risk patients.
Hypofractionated Radiotherapy in Breast Cancer.pptxAsha Arjunan
1) The document outlines studies evaluating hypofractionated whole breast radiotherapy (HF-WBI) for breast cancer treatment. The Ontario Clinical Oncology Group trial found local recurrence rates and overall survival were similar between HF-WBI (42.5 Gy in 16 fractions) and standard WBI (50 Gy in 25 fractions), with lower late toxic effects for HF-WBI.
2) The UK START trials also found similar local recurrence rates between HF-WBI schedules (39-41.6 Gy) and standard WBI (50 Gy), with lower normal tissue effects for HF-WBI. The UK FAST trial found mild/marked breast changes were higher for 30 Gy compared to 50 Gy but not for
This document summarizes recent developments in the treatment of head and neck cancer, focusing on the humanized monoclonal antibody nimotuzumab. A phase IIb clinical trial found that combining nimotuzumab with chemoradiation therapy significantly improved overall survival rates compared to chemoradiation alone. Specifically, the 5-year overall survival rate was 57% for patients receiving chemoradiation plus nimotuzumab, compared to only 26% for those receiving chemoradiation alone. Overall, the study demonstrates that nimotuzumab can be safely and effectively administered along with radiation therapy or chemoradiation therapy for advanced head and neck cancer.
Advances In Adjuvant Systemic Therapy Of Breast Cancerfondas vakalis
This document discusses adjuvant systemic therapy options for breast cancer. It provides an overview of chemotherapy, endocrine therapy, targeted therapy and radiotherapy approaches. It also discusses ongoing clinical trials evaluating newer adjuvant treatments and biomarkers to help determine optimal treatment approaches for individual patients.
The Oncotype DX test analyzes the activity of 21 genes from a breast cancer sample to calculate a recurrence score between 0-100. A score below 18 indicates a low risk of recurrence where chemotherapy benefits are small. A score of 18-30 is intermediate risk and it is unclear if chemotherapy benefits outweigh risks. A score above 31 has a high recurrence risk where chemotherapy benefits likely outweigh risks. The test helps predict the likelihood of disease recurrence and magnitude of chemotherapy benefit for node-negative breast cancer patients.
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- Several risk stratification models (UISS, SSIGN, Leibovich) are used to predict survival and guide surveillance and treatment eligibility.
- Early adjuvant trials of VEGF TKIs like sunitinib and sorafenib showed minimal improvement in disease-free survival at significant cost of toxicity.
- The KEYNOTE-564 trial showed significant improvement in disease-free survival for high-risk RCC patients treated with adjuvant pembrolizumab compared to placebo.
The document discusses evidence from randomized controlled trials on the use of postmastectomy radiotherapy (PMRT) for breast cancer patients. The key trials found that PMRT reduces locoregional recurrence rates from 30% to 10% and breast cancer mortality by 5% at 15 years. PMRT improved disease-free and overall survival rates particularly in patients with 4 or more positive lymph nodes. Modern radiotherapy techniques can help reduce risks of complications from PMRT.
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Pruebas genómicas de recurrencia en cáncer de mama - OncotypeDx y su entorno
1. Agosto 29, 2019
Bogotá, Colombia
Uso de Biomarcadores Genómicos para
Guiar Terapia Sistémica en EBC
Mauricio Lema Medina
Clínica de Oncología Astorga / Clínica SOMA, Medellín
4. The Oncotype DX Breast Recurrence
Score® Test
4
Tailoring Treatment for Early-Stage, ER-Positive, HER2-Negative
Breast Cancer in the Era of Precision Medicine
5. Adjuvant Therapy Recommendations for Breast Cancer in the Year 2000
……it is important to determine whether there are specific patient populations
for whom it is reasonable to avoid the administration of cytotoxic
chemotherapy. Unfortunately, very limited information is available to answer
this important question.
5
J Natl Cancer Inst. 2001.
6. NSABP B-20: Which ER-Positive Patients Benefit From Chemotherapy?
“…..statistical analyses failed to identify a
subgroup of patients with negative nodes
and ER-positive tumors who failed to
benefit from chemotherapy.“
Fisher et al. J Natl Cancer Inst. 1997.
Conclusions: When considered in conjunction with findings in other NSABP studies, results from B-20
indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, nodal status,
tumor size, or ER status, should be candidates for chemotherapy.
4-5% absolute benefit from chemotherapy
ER: estrogen receptor
TAM: tamoxifen
MFT: methotrexate, fluorouracil, tamoxifen
CMFT: cyclophosphamide, methotrexate, fluorouracil, tamoxifen
32-33% relative risk reduction with chemotherapy
6
7. Adjuvant Treatment Decisions Are Driven by Both Prognostic and
Predictive Factors
• Age
• Nodal status
• Tumor size
• Tumor Grade
• HER2
• ER/PR
• Other multigene signature assays
• Oncotype DX Breast Recurrence
Score® test
Prognostic factors: provide information on
outcomes (eg, recurrence rate)
• ER
• HER2
• Oncotype DX Breast Recurrence
Score test
Predictive factors: determine degree of
response to a specific therapy
7
Oncotype DX Breast Recurrence Score test is the only genomic assay that is both
prognostic and predictive of chemotherapy benefit
ER: estrogen receptor
PR: progesterone receptor
HER2: human epidermal growth factor receptor 2Ballman. J Clin Oncol. 2015.
8. Treatment Decisions in ER-Positive, Node-Negative Invasive Breast Cancer
The Oncotype DX Breast Recurrence
Score® Test
8
9. Oncotype DX Breast Recurrence Score® Test
Paik et al. N Engl J Med. 2004.
9
ER
PR
Bcl2
SCUBE2
GRB7
HER2
Ki-67
STK15
Survivin
Cyclin B1
MYBL2
Stromelysin 3
Cathepsin L2
GSTM1
CD68
BAG1
Beta-actin GAPDH RPLPO GUS TFRC
Estrogen Proliferation HER2 Invasion Others
5 Reference Genes
16 Breast Cancer–Related Genes
ORIGINAL CUTOFFS RS (0-100)
Low Risk RS (0-17)
Intermediate Risk RS (18-30)
High Risk RS (31-100)
10. The Recurrence Score® Prognostic Risk Groups Defined for
Distant Recurrence
NSABP B-14: First Validation Study for Prognosis in Node-Negative Patient Population
10
Paik et al. N Engl J Med. 2004.
Distant recurrence over time
10-year rate of recurrence = 6.8%*
95% CI: 4.0%, 9.6%
0 2 4 6 8 10 12 14 16
Years
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%Proportionwithoutdistantrecurrence
RS <18, n = 338
RS 18-30, n = 149
RS ≥31, n = 181
All Patients, n = 668
P < .001
10-year rate of recurrence = 14.3%
95% CI: 8.3%, 20.3%
10-year rate of recurrence = 30.5%*
95% CI: 23.6%, 37.4%
*10-year distant recurrence comparison between low- and high-risk groups: P <.001. RS: Recurrence Score result
11. The Breast Recurrence Score® Test Predicts Those Patients Who
Do and Do Not Derive Benefit From Chemotherapy
NSABP B-20: Second Validation Study for Prediction in Node-Negative Patient Population
Paik et al. J Clin Oncol. 2006. RS: Recurrence Score resultYears
PATIENTS WITH HIGH RS ≥31
28% absolute benefit from
tamoxifen + chemotherapy
Interaction P = 0.038
11
Events
12. 5-Year BCSS by Recurrence Score® Group in the SEER
Database (= 49,681)
Miller et al. ASCO 2017.
Patients with Recurrence Score results 11-17 and 18-25 have excellent 5-year BCSS rates that are
remarkably similar to BCSS rates in Recurrence Score group 0-10
BCSS: breast cancer–specific survival
12
13. 5-Year BCSS by Recurrence Score® Group and Reported
Chemotherapy Use in the SEER Population
13
Only small proportions of the RS results <1 (3%) and
RS results 11-17 (8%) groups reported CT use as ‘yes’
• 5-year BCSS was high, regardless of reported CT use
For the RS results 18-25 group, CT use reported as
‘yes’ was more common (29%)
• 5-year BCSS was 99% in this group, regardless of reported
CT use
For the RS results 26-30 and RS results ≥31 groups,
CT use reported as ‘yes’ was common
• 5-year BCSS was higher for those with CT use reported as
‘yes’ compared to ‘no/unknown’
BCSS: breast cancer–specific survival; RS: Breast Recurrence Score; CT: chemotherapyMiller et al. ASCO 2017.
14. TAILORx Takes the Oncotype DX Recurrence Score® Results to the
Next Level of Precision for Adjuvant Treatment Decisions
14
+
Prediction
of chemotherapy benefit
Prediction
of chemotherapy benefit
with precision for each patient
Prognosis
of disease
NSABP B-14 NSABP B-20 TAILORx
ORIGINAL CUTOFFS TREATMENT
Low (0-17) Endocrine (ET)
Intermediate (18-30) ET?
High (31-100) ET + chemo
RECURRENCE
SCORE
TREATMENT
Low (0-25) ET
High (26-100) ET + chemo
Sparano et al. J Clin Oncol. 2008.
15. 5-Year BCSS in the Recurrence Score® Results 26-30 and 31-100
Groups by Reported Chemotherapy Use in the SEER Population
Miller et al. ASCO 2017.
15
Though not a randomized population, there is a clear and significant difference in 5-year BCSS in
patients receiving CT with RS results 26-100, supporting results seen in NSABP B-20
BCSS: breast cancer–specific survival
16. Rationale for Investigating Chemotherapy Benefit in Intermediate
Oncotype DX Recurrence Score® Results
16
Paik et al. J Clin Oncol. 2006.
TAM: tamoxifen
CMF: cyclophosphamide, methotrexate and fluorouracil
MF: cyclophosphamide, methotrexate and fluorouracil
17. Rationale for Adjusting Midrange Recurrence Score® Result to
11-25 for TAILORx Trial
• Minimize potential for
undertreatment
• RS (0-10) represent an
approximately 10% risk of
distant recurrence and
considered a threshold for
recommending chemotherapy
• Preserve chemotherapy
prediction in high-risk group
17
Sparano et al. J Clin Oncol. 2008.
NSABP B-20: Relationship Between Continuous RS and Distant
Recurrence by Treatment RS: Recurrence Score result
TAM: tamoxifen
TAM
TAM + Chemo
18. Rationale for Adjusting Midrange Recurrence Score® Result to
11-25 for TAILORx Trial
NSABP B-20
18
Sparano et al. J Clin Oncol. 2008.
Significant chemotherapy benefit with RS ≥26 similar to RS result ≥31
Patients 10-Year DRFS (%)
Recurrence by Addition
of Chemotherapy
RS No. % TAM TAM + chemo HR 95% CI P
0-10 177 27 98 95 1.788 0.360 to 8.868 0.471
11-25 279 43 95 94 0.755 0.313 to 1.824 0.531
26-100 195 30 63 88 0.285 0.148 to 0.551 < 0.0001
DRFS: distant recurrence-free survival
RS: Recurrence Score result
TAM: tamoxifen
Absolute Benefit = 25% Relative Risk Reduction = 71%
19. TAILORx Methods: Treatment Assignment and Randomization
Accrued Between April 2006–October 2010
19
HR+/HER2-Negative Node-Negative Breast Cancer
Oncotype DX® Test
(N = 10,273)
Arm A: Low RS 0-10
ET
(N = 1629)
Midrange RS 11-25
RANDOMIZE
(N = 6711)
Arm D: High RS 26-100
ET + Chemo
(N = 1389)
Arm B: Experimental Arm
ET Alone
(N = 3399)
Arm C: Standard Arm
ET + Chemo
(N = 3312) ET: endocrine therapy
HR: hormone receptor
HER2: human epidermal growth factor receptor 2
RS: Recurrence Score® result
Stratification factors:
• Menopausal status
• Planned chemotherapy
• Planned radiation
• RS 11-15, 16-20, 21-25
Sparano et al. J Clin Oncol. 2008.
20. TAILORx Methods: Key Eligibility Criteria
Met NCCN Guidelines® for Recommending or Considering Adjuvant Chemotherapy
• Women with early-stage invasive breast cancer
• Age 18-75 years
• Node-negative
• ER- and/or PR-positive in local lab (before ASCO-CAP guidelines)
• HER2-negative in local lab
• Tumor size: 1.1-5.0 cm (or 0.6-1.0 cm and intermediate- or high-grade)
• Willing to have chemotherapy treatment assigned or randomized based on
Recurrence Score® results
20
Sparano et al. N Engl J Med 2018.
ER: estrogen receptor
PR: progesterone receptor
HER2: human epidermal growth factor receptor 2
ASCO: American Society of Clinical Oncology
CAP: College of American Pathologists
21. TAILORx Design: Statistical Analysis Plan for Recurrence Score®
Result 11-25 Group
• Primary endpoint was invasive disease-free survival (iDFS)
• Secondary endpoints included distant recurrence-free interval, relapse-free interval, and
overall survival
• Noninferiority design for randomized arms
• Arm B: experimental (endocrine therapy alone) compared to Arm C: standard
of care (chemoendocrine therapy)
• Final analysis after 835 prespecified iDFS events were reached
21
Sparano et al. N Engl J Med 2018.
22. TAILORx: Patient Characteristics for Recurrence Score® Result 11-25 Group
22
Sparano et al. N Engl J Med. 2018.
Characteristic
Recurrence Score
Result of 11-25
Endocrine
Therapy (n =
3399)
Chemoendocrine
Therapy
(n = 3312)
Median Age
(Range) – years
55
(23-75)
55
(25-75)
Tumor Size – cm
Median (IQR)
1.5
(1.2-2.0)
1.5
(1.2-2.0)
Tumor Grade
L – 29%
I – 57%
H – 13%
L – 29%
I – 57%
H – 14%
Clinical Risk
L – 74%
H – 26%
L – 73%
H – 27%
33% (N = 2216) ≤50 years
13% (N = 869) ≤1 cm (grade I/H)
63% (N = 4253) tumors 1-2 cm
24% (N = 1587) >2 cm
Clinical risk defined via modified Adjuvant! Online
• Low risk:
• Tumor size ≤3 cm and Grade 1
• Tumor size ≤2 cm and Grade 2
• Tumor size ≤1 cm and Grade 3
• High risk: All other cases with known values for
grade and tumor size
23. Patient Characteristics: Wide Range of Recurrence Score® Results
Seen Across Prognostic Clinicopathologic Features
23
Sparano et al. N Engl J Med 2018; ECOG (data on file).
Characteristic
All Patients
(n = 9719)
Recurrence Score
Result of 0-10
Recurrence Score
Result of 11-25
Recurrence Score
Result of 26-100
Endocrine Therapy
(n = 1619)
Endocrine
Therapy (n =
3399)
Chemoendocrine
Therapy
(n = 3312)
Chemoendocrine Therapy
(n = 1389)
Median Age
(Range) – years
56
(25-75)
58
(25-75)
55
(23-75)
55
(25-75)
56
(23-75)
Tumor Size – cm
Median (IQR)
1.5
(1.2-2.1)
1.5
(1.2-2.0)
1.5
(1.2-2.0)
1.5
(1.2-2.0)
1.7
(1.3-2.3)
Tumor Grade
L – 2512 (27%)
I – 5242 (56%)
H – 1676 (18%)
L – 34%
I – 59%
H – 7%
L – 29%
I – 57%
H – 13%
L – 29%
I – 57%
H – 14%
L – 7%
I – 43%
H – 50%
Clinical Risk
L – 6615 (70%)
H – 2812 (30%)
L – 78%
H – 22%
L – 74%
H – 26%
L – 73%
H – 27%
L – 43%
H – 57%
25% of patients with RS 0-25 have
clinical high-risk features
43% of patients with RS 26-100 have
clinical low-risk features
RS: Recurrence Score result
24. Age Distribution in TAILORx Patients Is Representative of
Invasive Breast Cancer Patients in the US Population
24
Sparano et al. N Engl J Med. 2018; SEER Database N-, HR+, HER2-.
TAILORx 2006-2010 SEER 2010*
Age
Distribution –
total no. (%)
RS 0-10 RS 11-25 RS 26-100 All Patients
9719 women 12836 women
≤40 years 58 (4%) 311 (5%) 79 (6%) 448 (5%) 654 (5%)
41-50 years 371 (23%) 1905 (28%) 330 (24%) 2606 (27%) 2700 (21%)
51-60 years 563 (35%) 2441 (36%) 512 (37%) 3516 (36%) 3631 (28%)
61-70 years 518 (32%) 1763 (26%) 395 (28%) 2676 (28%) 4250 (33%)
70-75 years 109 (7%) 291 (4%) 73 (5%) 473 (5%) 1601 (13%)
The frequency of younger patients is similar between TAILORx and SEER patients
*SEER patients reflect HR-positive, HER2-negative breast cancer patients with clinicopathologic characteristics consistent with women eligible for TAILORx.
RS: Recurrence Score® result
25. Tumor Size Distribution in TAILORx Patients Is Representative of
Invasive Breast Cancer Patients in the US Population
25
Sparano et al. N Engl J Med. 2018; SEER Database. N-, HR+, HER2-.
TAILORx 2006-2010 SEER 2010*
Tumor Size
Distribution –
total no. (%)
RS 0-10 RS 11-25 RS 26-100 All Patients
9719 women 12836 women
T1
≤1 cm
(grade 2/3)
202 (12%) 869 (13%) 188 (14%) 1259 (13%) 2258 (18%)
1.1-2.0 cm 1018 (63%) 4253 (63%) 741 (53%) 6012 (62%) 6674 (52%)
T2
2.1-3.0 cm 297 (18%) 1265 (19%) 348 (25%) 1910 (20%) 2413 (19%)
3.1-4.0 cm 83 (5%) 241 (4%) 91 (7%) 415 (4%) 762 (6%)
≥4.1 cm 19 (1%) 81 (1%) 20 (1%) 120 (1%) 729 (6%)
Distribution of tumor size is similar between TAILORx and SEER patients
*SEER patients reflect HR-positive, HER2-negative breast cancer patients with clinicopathologic characteristics consistent with women eligible for TAILORx.
RS: Recurrence Score® result
26. Tumor Grade Distribution in TAILORx Patients Is Representative
of Invasive Breast Cancer Patients in the US Population
26
TAILORx 2006-2010 SEER 2010*
Tumor Grade
Distribution –
total no. (%)
RS 0-10 RS 11-25 RS 26-100 All Patients
9719 women 12,530 women
Low 530 (34%) 1893 (29%) 89 (7%) 2512 (27%) 2748 (22%)
Intermediate 931 (59%) 3721 (57%) 590 (43%) 5242 (56%) 7100 (57%)
High 111 (7%) 884 (14%) 681 (50%) 1676 (18%) 2682 (21%)
Distribution of tumor grade is highly similar between TAILORx and SEER patients
Sparano et al. N Engl J Med. 2018; SEER Database. N-, HR+, HER2-.
*SEER patients reflect HR-positive, HER2-negative breast cancer patients with clinicopathologic characteristics consistent with women eligible for TAILORx.
RS: Recurrence Score® result
27. TAILORx Results: Systemic Treatments for Recurrence Score®
Results 11-25, Arms B & C (N = 6711)
• Endocrine therapy
• Comparable adherence and duration in both arms
• Extended endocrine therapy (>5 years) – 35%
• Postmenopausal – included aromatase inhibitor in 91%
• Premenopausal – included ovarian suppression in 13%
• Chemotherapy
• Most common regimens were taxane and cyclophosphamide (56%) and
anthracycline-containing (36%)
27
Sparano et al. N Engl J Med. 2018.
29. TAILORx Results: Endocrine Therapy Alone Was Not Inferior to
Chemoendocrine Therapy in Patients With RS 11-25 (Arms B & C)
Primary Endpoint: 9-Year Invasive Disease-Free Survival (iDFS) in ITT Population
836 iDFS events after
median follow-up of
7.5 years
29
ITT: intent-to-treat
iDFS: invasive disease-free survival
RS: Recurrence Score® results
ET: endocrine therapySparano et al. N Engl J Med. 2018.
30. TAILORx Results: Patients With RS 11-25 (Arms B & C) Have a
Very Low Risk of Distant Recurrence
Secondary Endpoint: 9-Year Distant Recurrence-Free Interval in ITT Population
199 of 836 (23.8%)
were distant
recurrences
30
Sparano et al. N Engl J Med. 2018.
ITT: intent-to-treat
DRFI: distant recurrence-free interval
RS: Recurrence Score® result
ET: endocrine therapy
31. TAILORx Results: Patients With RS 11-25 on Endocrine Therapy Alone (Arm B)
Have Equivalent Outcomes to Those on Chemoendocrine Therapy (Arm C)
Other Secondary Endpoints: ITT Population
31
RFI: relapse-free interval
OS: overall survival
ITT: intent-to-treat
RS: Recurrence Score® result
ET: endocrine therapy
Sparano et al. N Engl J Med. 2018.
32. TAILORx Results: Patients in Arms A, B & C With RS 0-25 Have ≤5%
Risk of Distant Recurrence at 9 Years
9-Year Event Rates – ITT Population: All Arms
32
ET: endocrine therapy
ITT: intent-to-treat
RS: Recurrence Score® resultSparano et al. N Engl J Med. 2018.
Patients in Arm D experienced a
higher rate of distant recurrence
at 13% despite
chemoendocrine therapy
33. TAILORx Results: Exploratory Analysis in Clinical Subgroups to
Identify Chemotherapy Benefit in Recurrence Score®
Results 11-25
• Exploratory interaction tests were performed for subgroups that may derive chemotherapy benefit in
the Recurrence Score 11-25 group (ITT population)
• Exploratory analysis subgroups:
• Recurrence Score subgroups 11-15 vs 16-20 vs 21-25; 11-17 vs 18-25
• Clinicopathologic subgroups: tumor size, tumor grade, clinical risk category
• Menopausal status
• Age
33
Sparano et al. N Engl J Med. 2018. ITT: intent-to-treat
34. TAILORx Results: Exploratory Analysis of Chemotherapy
Treatment Interactions in Recurrence Score® Results 11-25 Arms
34
Recurrence Score result
11-15 vs 16-20 vs 21-25
11-17 vs 18-25
Tumor size (≤2 cm vs >2 cm)
Grade (low vs int vs high)
Menopausal status (pre vs post)
Clinical risk category (high vs low)
Sparano et al. N Engl J Med. 2018.
No statistically significant chemotherapy treatment interactions were found in any
of these subgroups
35. TAILORx Results: Exploratory Analysis of Chemotherapy
Treatment Interactions in Recurrence Score® Results 11-25
35
• There was a statistically significant chemotherapy treatment interaction with patient age
and Recurrence Score (RS) for invasive disease-free survival and recurrence-free interval
• Some chemotherapy benefit was seen in patients age ≤50 who had RS results 16-20 and RS
results 21-25
• There was no statistically significant chemotherapy treatment interaction seen with patient
age and RS results for distant recurrence-free interval
Invasive disease–free survival defined as the first event of distant recurrence, local–regional recurrence,
contralateral breast or other second primary cancer, or death without cancer recurrence.
Recurrence-free interval defined as all distant and local recurrences.
Distant recurrence-free interval defined as distant recurrences only.Sparano et al. N Engl J Med. 2018.
36. TAILORx Results: A Small Chemotherapy Benefit Is Seen in Women
≤50 Years (N = 3054) With Recurrence Score® Results 16-20 and 21-25
9-Year Freedom From Distant Recurrence
36
Sparano et al. N Engl J Med. 2018.
ITT: intent-to-treat
ET: endocrine therapy
CT: chemotherapy
RS: Recurrence Score results
*These differences in distant recurrences, while not statistically significant, may be clinically significant.
* *
37. Implications for Clinical Practice Based on TAILORx Definitive
Results Using the Oncotype DX Breast Recurrence Score® Test
37
Recurrence Score Result
0-25 26-100
No Chemotherapy Benefit Chemotherapy Benefit
Node-negative, HR-positive, HER2-negative
HR: hormone receptor
HER2: human epidermal growth factor receptor 2Sparano et al. J Clin Oncol. 2008.
38. TAILORx: The Prediction of Chemotherapy Benefit With the
Oncotype DX Breast Recurrence Score® Test Is Largely Binary for
Patients >50 Years
Node-negative, HR-positive, HER2-negative
38
Sparano et al. J Clin Oncol. 2008; Genomic Health (data on file). RS distributions in tested US N-, HR+, HER2- patients in 2017.
Subgroup Age >50 years
RS 0-10
No CT Benefit
RS 11-15
No CT Benefit
RS 16-20
No CT Benefit
RS 21-25
No CT Benefit
RS 26-100
CT Benefit
~85% of patients ~15% of patients
CT: chemotherapy
HR: hormone receptor
HER2: human epidermal growth factor receptor 2
RS: Recurrence Score result
39. TAILORx: Precise Determination of Potential Chemotherapy Benefit
for Patients ≤50 Years With Breast Recurrence Score® Test
Node-negative, HR-positive, HER2-negative
39
CT benefit for distant recurrence from Sparano 2018 ASCO presentation; Sparano et al. J Clin Oncol. 2008; Genomic Health (data on file). RS
distributions in tested US N-, HR+, HER2- patients in 2017.
Subgroup Age ≤50 years
RS 0-10
No CT Benefit
RS 11-15
No CT Benefit
RS 16-20
~1.6% CT Benefit
RS 21-25
~6.5% CT Benefit
RS 26-100
CT Benefit
~50% of patients ~23% of patients ~12% of patients ~15% of patients
CT: chemotherapy
HR: hormone receptor
HER2: human epidermal growth factor receptor 2
RS: Recurrence Score result
40. Prospective Validation of the Oncotype DX Breast Recurrence
Score® (RS) Test in TAILORx Provides the Highest Level of
Evidence for Adjuvant Treatment Decisions
• The TAILORx study utilized the Oncotype DX Breast Recurrence Score test to
definitively prove that HR-positive, HER2-negative, node-negative patients with
RS results 0-25 do not benefit from chemotherapy
• Safely spares patients with RS results 0-25 from overtreatment, as they have excellent
outcomes with endocrine therapy alone
• Provides information on potential chemotherapy benefit for patients ≤50 years with
RS results 16-25
• Prognostic subgroups studied in TAILORx (ie, tumor size, tumor grade) do NOT
predict who will or will not benefit from chemotherapy
• Consistent findings with NSABP B-20 confirm recommendations for adjuvant
chemotherapy for patients with RS results 26-100 eliminating risk
for undertreatment
40
Paik et al. J Clin Oncol. 2006.; Sparano et al. J Clin Oncol. 2008.; Sparano et al. N Engl J Med. 2018.
42. Quantitative ER Expression Is Only Modestly Correlated With
Recurrence Score® Results
Many highly ER-expressing tumors have Recurrence Scores 26-100
Kim et al. J Clin Oncol. 2011. ER: estrogen receptor
42
43. Clalit Registry: Using Clinical or Pathologic Factors to Determine Treatment
Can Result in Significant Under and Overtreatment
Characteristic (N = 1801)
RS 0-25
N = 1442 (80.1%)
RS 26-100
N = 359 (19.9%)
Age – years <50 (N = 295)
50-69 (N = 1184)
≥70 (N = 322)
226 (76.6%) 69 (23.4%)
959 (81%) 225 (19%)
257 (79.8%) 65 (20.2%)
Tumor Size – cm ≤1 (N = 400)
>1-2 (N = 996)
>2 (N = 393)
Unknown (N = 12)
346 (86.5%) 54 (13.5%)
803 (80.6%) 193 (19.4%)
284 (72.3%) 109 (27.7%)
9 3
Tumor grade 1 (N = 258)
2 (N = 907)
3 (N = 297)
Unknown/not applicablea (N = 339)
243 (94.2%) 15 (5.8%)
747 (82.4%) 160 (17.6%)
164 (55.2%) 133 (44.8%)
288 51
43
a59.8% of unknown tumor grade are invasive lobular carcinoma.Stemmer et al. npj Breast Cancer. 2017.
ER: estrogen receptor
RS: Recurrence Score® result
44. West German Study Group PlanB Study: A Distribution of Recurrence Score®
(RS) Results Seen Within All Ranges of Ki-67 Expression
Gluz et al. J Clin Oncol. 2016.
44
RS results had a week to
moderate positive correlation
with Ki-67
• RS results >25 are found in
samples with Ki-67 <20%
• RS results ≤25 found in
samples with Ki-67 >39%
Ki-67 expression is not
predictive of
chemotherapy benefit
45. The Breast Recurrence Score® Test Can Identify Patients With Favorable
Histologic Subtypes With Recurrence Scores® Results >25 That Could Benefit
From Chemotherapy
Tadros et al. Ann Surg Oncol. 2018.
45
N = 504,362 N = 49,819 N = 5,069 N = 25,329 N = 16,116 N = 4,159 N = 3,599 N = 1,897
3.2 – 12.1% of tumors
with favorable
histologic subtypes
have Recurrence Score
results >25
46. TAILORx: Clinicopathologic Features Do Not Predict
Chemotherapy Benefit
Characteristics Predictive of Chemotherapy Benefit?
Tumor size (≤2 cm vs >2 cm) No
Grade (low vs int vs high) No
Menopausal status (pre vs post) No
Clinical risk category (high vs low) No
TAILORx confirmed that clinicopathologic subgroups are not predictive
of chemotherapy benefit. Only the Breast Recurrence Score® test is both
prognostic and predictive of the magnitude of chemotherapy benefit
Sparano et al. N Engl J Med. 2018.
46
47. Clinical Risk*
Low High
Recurrence
Score
Results
0-25
(n = 8068)
75% 25%
26-100
(n = 1359)
43% 57%
TAILORx: Oncotype DX Breast Recurrence Score® Prevents Over-
and Undertreatment of Patients
47
Sparano et al. N Engl J Med. 2018.
Would have been
overtreated
*Low clinical risk defined by low grade and tumor size ≤ 3 cm, intermediate grade and tumor size ≤2 cm, and high grade and tumor size ≤1 cm;
high clinical risk defined as all other cases with known values for grade and tumor size.
Would have been
undertreated
48. Oncotype DX Breast Recurrence Score® Test Is the Only
Predictive Biomarker That Identifies the Right Treatment for the
Right Patient
• Clinical and pathologic factors are not predictive of chemotherapy benefit
• Oncotype DX Breast Recurrence Score test is the only biomarker shown to be
predictive of the magnitude of chemotherapy benefit
• There is only modest correlation between clinical or pathologic factors and the
Recurrence Score® result
• The Recurrence Score result identifies those patients in which tumor biology is
discordant with clinical and pathologic factors, providing definitive prognostic and
predictive information for adjuvant treatment decisions and avoiding under-
or overtreatment
48
49. The Oncotype DX Breast Recurrence Score® Test
49
Current Guideline and Staging
Recommendations
50. 7th Edition Stage
Tumor Size
Nodal
Involveme
nt
Metastasis
2010-2017
Application of the New Staging Criteria to Breast Cancer
Creation of Prognostic Stage Groups Using Biomarkers
Hortobagyi et al. AJCC Cancer Staging Manual. 8th ed. https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx. Accessed January 17, 2018.
50
51. Inclusion of Oncotype DX Breast Recurrence Score® Test
into AJCC 8th Edition Staging Manual
When Oncotype DX Score is less than 11…*
51
Hortobagyi et al. AJCC Cancer Staging Manual. 8th ed. https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx. Accessed January 17, 2018.
When TNM is… And G is… And HER2 Status is… And ER Status is… And PR Status is…
The Prognostic Stage
Group is…
T1 N0 M0
T2 N0 M0
Any Negative Positive Any IA
*If available.
“Oncotype DX® is the only multigene panel included to classify Pathological Prognostic
Stage because prospective Level I data support this use for patients with a score <11.”
(Emphasis added.)
— AJCC 8th Edition Cancer Staging Manual (Second Revision)
53. Possible Considerations for Guideline and Staging Updates Based
on TAILORx Results in HR-Positive/HER2-Negative, Node-Negative
Breast Cancer Patients
• AJCC Staging: TAILORx provides current prognostic information for patients
treated with standard of care adjuvant therapies based on the
Recurrence Score® result
• 9-year distant recurrence ≤5% for RS 0-25 on endocrine therapy alone
• 9-year distant recurrence 13% for RS 26-100 on chemoendocrine therapy
• Treatment guidelines for the adjuvant setting
• Remove intermediate scores
• Endocrine therapy alone for RS 0-25
• Chemoendocrine therapy for RS 26-100
• Discuss chemotherapy options and potential benefit in patients ≤50 years with RS 16-25
53
Paik et al. J Clin Oncol. 2006; Sparano et al. J Clin Oncol. 2008; Sparano et al. N Engl J Med. 2015; Sparano et al. N Engl J Med. 2018.
HR: hormone receptor
HER2: human epidermal growth factor receptor 2
RS: Recurrence Score result
54. Overview of Available Multigene Assays
How Do They Compare With the Oncotype DX Breast Recurrence Score® Test?
54
55. Prognostic Versus Predictive Biomarkers
• Prognostic biomarkers: A prognostic biomarker provides information on a
cancer outcome (eg, disease recurrence, disease progression)
• Predictive biomarkers: A biomarker is predictive if the treatment effect is
different for biomarker-positive patients compared with biomarker-
negative patients
• At least 2 comparison groups are needed (eg, 2 different treatment arms in a
randomized trial)
• Examples: HER2, ER
• To determine whether a biomarker is potentially predictive, a formal test for
an interaction between the biomarker, treatment group, and outcome must
be statistically significant (P <0.05)
Ballman. J Clin Oncol. 2015.
ER: estrogen receptor
HER2: human epidermal growth factor receptor 2
55
57. Genomic Tests for Breast Cancer Are NOT the Same
Commercially Available Tests Are Not Interchangeable
1. Paik et al. N Engl J Med. 2004.; 2. Paik et al. J Clin Oncol. 2006.; 3. Bueno-de-Mesquita et al. Lancet Oncol. 2007.; 4. Mook et al. Breast Cancer Res Treat. 2009.; 5. Sapino et al. J Mol Diagn. 2013.
Oncotype DX® (21-gene assay) MammaPrint® (70-gene assay)
Quantitative gene expression by RT-PCR Microarray
Clinical validation populations: homogeneous
with inclusion of standard of care adjuvant endocrine
therapy when reporting recurrence risk
Clinical validation populations: heterogenous
without consideration of standard of care adjuvant
endocrine therapy in reporting recurrence risk
Prospectively validated for prognosis Prospectively validated for prognosis
Validated for predicting therapy benefit:
• Lack of chemotherapy benefit (RS 0-25)
• Significant chemotherapy benefit (RS 26-100)
• Endocrine therapy benefit based on quantitative ESR1
expression (ER)
No evidence for chemotherapy or endocrine
therapy prediction
Results provide:
Prognosis: Continuous score provides individualized
risk of recurrence
Prediction: Largely binary result for chemotherapy
prediction
Results provide:
Prognosis: Binary result as low/high-risk group with no
individualized risk estimate
Prediction: None
RS: Recurrence Score® result
57
58. MammaPrint® Prognosis Profile From Validation Study
van’t Veer et al. Nature. 2002; van de Vijver et al. N Engl J Med. 2002.
MammaPrint Low Risk:
A “low-risk” MammaPrint result means that
a patient has on average a 10% chance
that her cancer will recur within 10 years
without any additional adjuvant treatment,
either hormonal therapy or chemotherapy.
MammaPrint High Risk:
A “high-risk” MammaPrint result means
that a patient has a 29% chance that her
cancer will recur within 10 years without
any additional adjuvant treatment, either
hormonal therapy or chemotherapy.
MammaPrint does not provide the individual’s risk of
recurrence. How low or high is their risk?
58
59. Subset of MammaPrint® Prognostic Validation Studies in
Heterogeneous Patient Populations
Study
Pre-
menopausal
Post-
menopausal
ER+ ER- LN+ LN- Prospective
van de Vijver. N Engl J Med. 2002
(n = 295)
X X X X X
Buyse J. Natl Cancer Inst. 2006
(n = 307)
X X X X
Bueno-de-Mesquita. Lancet Oncol. 2007
(n = 427)
X X X X X
Mook. Breast Cancer Res Treat. 2009
(n = 241)
X X X
Wittner. Clin Cancer Res. 2008 (n = 100) X X X X X
Mook. Ann Oncol. 2010 (n = 148) X X X X X
Cardoso. N Engl J Med. 2016
(n = 1550)*
X X X X X X X
Adapted from Hyams et al. J Surg Oncol. 2016.
*High clinical risk/low genomic risk target population.
ER: estrogen receptor
LN: lymph node
AET: adjuvant endocrine therapy
ACT: adjuvant chemotherapy
59
61. MINDACT Results Summary
• The primary objective was met: patients with high clinical risk, low genomic risk
(by MammaPrint®) had a 5-year DMFS rate of 94.7% (95% CI, 92.5 to 96.2) without
chemotherapy
• Patients identified as Genomic High Risk by MammaPrint randomized to
chemotherapy did not show a therapeutic benefit
• Patients identified as Genomic Low Risk by MammaPrint randomized to
chemotherapy did show a consistent therapeutic benefit
• Results with node-positive patients with high clinical risk, low genomic risk are not
clear or definitive
61
Cardoso et al. N Engl J Med. 2016. DMFS: distant metastasis-free survival
62. MINDACT: Study Design
Enrollment
N=6693
Clinical Risk (C)
Adjuvant! Online
Genomic Risk (G)
70-gene signature
MammaPrint® (MMPT)
C-low/G-low (MMPT low)
N=2745
C-low/G-high (MMPT high)
N=592
C-high/G-low (MMPT low)
N=1550
C-high/G-high (MMPT high)
N=1806
Discordant
Randomized ChemotherapyNo Chemotherapy
Modified from Cardoso et al. N Engl J Med. 2016.
“We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene
signature to standard clinical–pathological criteria in selecting patients for adjuvant chemotherapy.”
62
65. MINDACT Primary Objective Defined
• In patients with high clinical risk, low genomic risk (MammaPrint® low), and
who did not receive chemotherapy:
• Is the lower boundary of the 95% confidence interval for the rate of
5-year distant metastasis-free survival 92% (ie, the noninferiority
boundary) or higher?
Cardoso et al. N Engl J Med. 2016.
Though discordant groups were randomized to endocrine
therapy alone or chemoendocrine therapy, the primary
objective was NOT to determine who does or does not
benefit from chemotherapy
65
66. MINDACT: Enrollment and Risk Groups Included in the Analyses
Only 644 out of 6693 Patients Were Used in the Primary Analysis
Modified from Cardoso et al. N Engl J Med. 2016.
Enrollment
N = 6693
344 assigned to
receive chemo
346 not assigned to
receive chemo
2634 had C-low and G-
low at enrollment
(2745*)
690 had CLINICAL LOW RISK
and genomic high risk at
enrollment (592*)
1497 had CLINICAL HIGH RISK
and Genomic low risk at
enrollment (1550*)
1873 had C-high and
G-high at enrollment
(1806*)
*Number of patients in this group after lab
error correction applied
R
749 assigned to
receive chemo
748 not assigned to
receive chemo
R
53 had a change in
risk
42 received
chemotherapy
4 were ineligible
57 had a change in risk
76 received chemotherapy
5 had unknown chemotherapy
status
4 were ineligible
26 had a change in
risk
128 received
chemotherapy
9 had unknown
chemotherapy status
11 were ineligible
21 had a change in
risk
85 received
chemotherapy
1 had unknown
chemotherapy status
12 were ineligible
224 were included in
the per-protocol
population
254 were included in
the per-protocol
population
592 were included in
the per-protocol
population
636 were included in
the per-protocol
population
644 were included
in the primary-test
population
Per protocol
population
Genomic high (G-high): MammaPrint® high risk
Genomic low (G-low): MammaPrint low risk
66
67. MINDACT: Enrollment and Risk Groups Included in the Analyses
Only 644 out of 6693 Patients Were Used in the Primary Analysis
Modified from Cardoso et al. N Engl J Med. 2016.
Enrollment
N = 6693
344 assigned to
receive chemo
346 not assigned to
receive chemo
2634 had C-low and G-
low at enrollment
(2745*)
690 had CLINICAL LOW RISK
and genomic high risk at
enrollment (592*)
1497 had CLINICAL HIGH RISK
and Genomic low risk at
enrollment (1550*)
1873 had C-high and
G-high at enrollment
(1806*)
*Number of patients in this group after lab
error correction applied
R
749 assigned to
receive chemo
748 not assigned to
receive chemo
R
53 had a change in
risk
42 received
chemotherapy
4 were ineligible
57 had a change in risk
76 received chemotherapy
5 had unknown chemotherapy
status
4 were ineligible
26 had a change in
risk
128 received
chemotherapy
9 had unknown
chemotherapy status
11 were ineligible
21 had a change in
risk
85 received
chemotherapy
1 had unknown
chemotherapy status
12 were ineligible
224 were included in
the per-protocol
population
254 were included in
the per-protocol
population
592 were included in
the per-protocol
population
636 were included in
the per-protocol
population
644 were included
in the primary-test
population
Intent-to-treat
population
Per protocol
population
Genomic high (G-high): MammaPrint® high risk
Genomic low (G-low): MammaPrint low risk
67
68. Patient Characteristics
Clinical High/Genomic Low
(MammaPrint® Low) Risk
(N=1550)*
TAILORx Recurrence
Scores® 11-25
(N=6711)
Age - yr
<50
≥50 to 70
>70
34.5% (N=534)
64.5% (N=1000)
1% (N=16)
33% (N=2216)
62.5% (N=4204)
4.5% (N=291)
Tumor size
<1 cm
1-2 cm
>2 cm
2.5% (N=38)
39.4% (N=610)
58.1% (N=843)
13% (N=869)
63% (N=4253)
24% (N=1587)
Tumor grade
Grade 1
Grade 2
Grade 3
6.3% (N=98)
64.2% (N=995)
28.6% (N=443)
29% (N=1893)
57% (N=3721)
14% (N=884)
Lymph node status
N0
N1
N2
52.4% (N=812)
47.2% (N=732)
0.4%(6)
100% (N=6711)
0%
0%
Hormone receptor
status
ER+, PR+ or both
ER- and PR-
98.1% (N=1520)
1.9% (N=29)
100% (N=6711)
0%
HER2 status%
HER2-
HER2+
91.8% (N=1423)
8% (N=124)
100% (N=6711)
0%
Patient Populations: TAILORx Has a Larger, Homogenous Patient Population
Compared to MINDACT
*Patient characteristics are not provided for the primary test population (N=644).
Cardoso et al. N Engl J Med. 2016.
ER: estrogen receptor
HER2: human epidermal growth factor receptor 2
PR: progesterone receptor
68
69. Click to edit Master title style Click to edit Master title style
MINDACT: Primary Objective Was Met
5-Year Rate of Distant Metastasis–Free Survival (DMFS)
Primary Objective:
In patients with high clinical risk, low genomic
risk (no chemotherapy), is the lower boundary
of the 95% confidence interval (CI) for the
rate of 5-year DMFS 92% or higher?
Yes, patients not treated with chemotherapy
(CT) had a 5-year DMFS rate of: 94.7% (95%
CI, 92.5 to 96.2)
Heterogeneous primary test population:
• N0, N1, N2
• ER/PR+, ER-/PR-
• HER2+ & HER2-
Cardoso et al. N Engl J Med. 2016.; Piccart et al. AACR. 2016.
ER: estrogen receptor
HER2: human epidermal growth factor receptor 2
PR: progesterone receptor
CI: confidence interval
69
71. Clinical Risk Group Definitions in MINDACT
Clinical risk was defined in the MINDACT trial via a modified Adjuvant! Online score
HR-positive, HER2-negative, node-negative
Low-risk:
Tumor size <3 cm and Grade 1
Tumor size <2 cm and Grade 2
Tumor size <1 cm and Grade 3
High-risk:
All other cases with known values for grade and tumor size
Cardoso et al. N Engl J Med. 2016.
HR: hormone receptor
HER2: human epidermal growth factor receptor 2
71
72. MINDACT: MammaPrint® Has Not Been Show to be Predictive of
Chemotherapy Benefit in Node-Negative Patients – ITT Population
Cardoso et al. N Engl J Med. 2016.
DMFS: distant metastasis–free survival
ITT: intent-to-treat population
CT: chemotherapy
CI: confidence interval
N=666 patients
Despite high-risk MammaPrint results,
patients receive no benefit from
chemotherapy
Despite low-risk MammaPrint results,
patients show a trend towards chemotherapy
benefit (31% risk reduction)
N=787 patients
(MammaPrint Low) (MammaPrint High)
72
73. Low-Risk MammaPrint® Patients Showed a Consistent Improvement When
Randomized to Chemotherapy – ITT Population
Clinical High-Risk/Genomic Low-Risk (MammaPrint® Low)
29% relative risk reduction
Cardoso et al. N Engl J Med. 2016.
Chemotherapy
No Chemotherapy
Year Disease-Free Survival CT
Patients
(N)
Events
(O)
% at 5 yr
(95% CI)
Hazard Ratio
(95% CI)
P-value
Clinical high-risk Yes 749 54 92.9 (90.5-94.7) 0.71 (0.50-1.01) 0.055
MammaPrint low-risk No 748 78 90.1 (87.5-92.1) 1.00
MammaPrint low-risk patients
experience a disease-free
survival benefit from
chemotherapy
~3%
absolute benefit
ITT: intent-to-treat population
CT: chemotherapy
CI: confidence Interval
73
74. Patients With Low-Risk MammaPrint® Results Showed a
Consistent Improvement When Randomized to Chemotherapy
Risk Group, Outcome,
and Treatment Strategy*
Chemotherapy
No. of
Patients
No. of
Events
Percentage With Outcome
of 5 Years (95% CI)
Hazard Ratio
(95% CI)
P-Value
Clinical high-risk and
genomic low-risk
DMFS 35% relative risk reduction
Clinical high-risk Yes 592 22 96.7 (94.7-98.0) 0.65 (0.38-1.10) 0.11
MammaPrint low-risk No 636 37 94.8 (92.6-96.3) 1.00
Disease-free survival
Clinical high-risk Yes 592 39 93.3 (90.7-95.2) 0.64 (0.43-0.95) 0.03
MammaPrint low-risk No 636 66 90.3 (87.6-92.4) 1.00
Overall survival
Clinical high-risk Yes 592 10 98.8 (97.4-99.5) 0.63 (0.29-1.37) 0.25
MammaPrint low-risk No 636 18 97.3 (95.6-98.4) 1.00
Adapated from Cardoso et al. N Engl J Med. 2016.
*Per-protocol population. CI: confidence interval
DMFS: distant metastasis-free survival
74
75. MammaPrint® 2017 ASCO® Guidelines Based on MINDACT Data
Guideline Patient Population Recommendation
1.1.1 ER/PR+, HER2-, node-negative, high
clinical risk
May use to withhold adjuvant systemic chemotherapy
1.1.2 ER/PR+, HER2-, node-negative,
low clinical risk
Should not be used to withhold adjuvant systemic chemotherapy
(did not appear to benefit even with genomic high risk)
69% of HR+/HER2-/node-negative patients included in MINDACT
were clinically low risk and not eligible for MammaPrint® testing
Only 30.9% of HR+/HER2-/node-negative patients included in MINDACT were
clinically high risk and eligible for MammaPrint® testing
Krop et al. J Clin Oncol. 2017.; Cardoso et al. N Engl J Med. 2016.
ER: estrogen receptor
PR: progesterone receptor
HR: hormone receptor
HER2: human epidermal growth factor receptor 2
75
76. Study Comparison – MINDACT & TAILORx
In ER-Positive, HER2-Negative, Node-Negative Patients
TAILORx MINDACT
Primary Objective Randomized Chemo Benefit Prognosis
Evaluable Patients (Primary Objective) 6711 350
Clinical Risk (%)
Low
High
75%
25%
69%
31%
Genomic Risk (%)
Low
High
86%
14%
75%
25%
Median Follow-up (years) 7.5 5.0
Reported Outcomes (years) 9 5
Sparano et al. N Engl J Med. 2018; Cardoso et al. N Engl J Med. 2016.
ER: estrogen receptor
HER2: human epidermal growth factor receptor 2
76
77. Risk Stratification by Oncotype DX Breast Recurrence Score® and
MammaPrint® in the Same Patient Cohorts
Assay Concordance
77
78. 82.1%
36.1%
61.4%
29.4%
17.9%
34.5%
38.6%
OPTIMA Study Stratified Risk Comparing Oncotype DX Breast
Recurrence Score® Test With Other Prognostic Multigene Assays
in the Same Patients
Oncotype DX
Breast Recurrence
Score assay
0-25 26-100Recurrence Score® (RS) results:
Low Intermediate HighRisk categories:
Prosigna
MammaPrint
Adapted from: Bartlett et al. J Natl Cancer Inst. 2016.
Pooled risk group distributions, N = 313 early-stage breast, node-negative and node-positive cancer patients
MammaPrint® assigns a substantially larger number of patients as high-risk
compared to Oncotype DX test, resulting in overtreatment with chemotherapy
Low Risk High RiskMammaPrint results:
78
79. Multigene Assays Do Not Classify Patients in The Same Way
MammaPrint® (genomic risk)
Low-Risk High-Risk Total
Oncotype DX Breast
Recurrence Score® (RS) test
RS 0-25 (Low) 177 70 247
RS 26-100 (High) 6 44 50
Total 183 114 297
Of 247 “low-risk” patients by RS result, 70 (28%) are high-risk by MammaPrint
Potential for
overtreatment
Of 50 “high-risk” patients by RS result, 6 (12%) are low-risk by MammaPrint
Potential for
undertreatment
Concordance between the two assays is 74%;
MammaPrint consistently classifies more patients as high risk
79
Adapted from: Bartlett et al. J Natl Cancer Inst. 2016.
80. Many Patients Stratified as High Risk by MammaPrint® Have High
Estrogen Receptor (ER) Expression by Oncotype DX Breast
Recurrence Score® Test
Poulet et al. SABCS 2012.
Many patients with high ER expression
and low-risk Oncotype DX Recurrence
Score® results are classified as high
risk by MammaPrint
MammaPrint high-risk classification is
not based on ER expression or
standard-of-care treatment with
adjuvant endocrine therapy
Patients stratified as high risk by
MammaPrint with high quantitative ER
expression may have a low risk of
recurrence with appropriate hormone
therapy
ER Expression by MammaPrint Risk Category
High
Intermediate
Low
Recurrence
Score Result
80
81. Multiple Studies Consistently Show MammaPrint® Classifies
37%-56% of ER-Positive, HER2-Negative Patients as “High Risk”
Denduluri et al. J Clin Oncol. 2011.; Cloughet al. St. Gallen 2013.; Shivers et al. SABCS 2013.; Marounet al. J Clin Oncol. 2015.; Dabbs et al. J Clin Oncol. 2017.; Tsai et al. Jama Oncol. 2017.
Denduluri 2011
56%
High risk
Clough 2013
39%
High risk
Shivers 2013
47%
High risk
Maroun 2015
43%
High risk
Dabbs 2017
37%
High risk
Tsai 2017
56%
High risk
MammaPrint has NOT been proven to be predictive of chemotherapy benefit and
overclassifies patients as high risk, resulting in overtreatment with chemotherapy
81
83. Genomic Assays for Breast Cancer Are NOT the Same
Commercially Available Tests Are Not Interchangeable
1. Paik et al. N Engl J Med. 2004.; 2. Paik et al. J Clin Oncol. 2006.; 3. Filipits et al. Clin Cancer Res.2011
Oncotype DX® (21-gene assay) EndoPredict® (12-gene assay)
Quantitative gene expression by RT-PCR Quantitative gene expression by RT-PCR
Recurrence Score® (RS) – calculated from
gene expression only
EPclin® Risk Score – calculated from a
combination of gene expression, tumor size,
and nodal status
Prospectively validated for prognosis Validated for prognosis (no prospective data)
Validated for predicting therapy benefit:
• Lack of chemotherapy benefit (RS 0-25)
• Significant chemotherapy benefit (RS 26-100)
• Endocrine therapy benefit based on quantitative
ESR1 expression (ER)
No evidence for chemotherapy or endocrine
therapy prediction
Results provide:
Prognosis: Continuous score provides
individualized risk of recurrence
Prediction: Largely binary result for
chemotherapy prediction
Results provide:
Prognosis*: Continuous score provides
individualized risk of recurrence
Prediction: None
*Node-negative & -positive patients grouped in one report.
83
84. Endopredict® EPclin Algorithm Is Strongly Influenced by
Nodal Status
EPclin Risk Score = 0.35 T + 0.65 N + 0.28 (EP)
T = 1 for ≤1 cm
T = 2 for 1–2 cm
T = 3 for 2–5 cm
T = 4 for >5 cm
N = 1 for N0
N = 2 for 1–3 nodes
N = 3 for 4–10 nodes
N = 4 for >10 nodes Reports classify prognosis within a mixed
N0-N2 population as “High- vs Low-Risk”
Tumor size
(Factor 1-4)
Nodal status
(Factor 1-4)
EP Molecular Score
EP Molecular
Score
(Factor 0-15)
The Oncotype DX Breast Recurrence Score® test is highly prognostic based on tumor
biology alone; additional prognostic factors are not required
Brase et al. Microarrays. 2013.
84
85. EndoPredict® Prognostic Validation Studies
Postmenopausal only;
32% are N+ patients
54% premenopausal;
N+ only
There are no validation data in N0 premenopausal patients or in
premenopausal patients treated with endocrine therapy alone
Buus et al.
comparison with
Oncotype DX®
ER: estrogen receptor
HER2: human epidermal growth factor receptor 2
N0: node-negative
N+: node-positive
85
Flipits et al. Clin Cancer Res. 2011; Martin et al. Breast Cancer Res. 2014; Buus et al. J Natl Cancer Inst. 2016.
86. Does EndoPredict® Provides Clarity on Adjuvant Therapy
Decisions?
• Relies on pathologic features for prognosis, most heavily on nodal status
• Vast majority of all node-positive patients are high-risk
• No prospective data
• Not shown to be predictive of chemotherapy benefit
• No data in node-negative premenopausal patients or with endocrine therapy alone
In node-negative patients and those with 1-3 positive nodes,
Oncotype DX Breast Recurrence Score® is highly prognostic based on
genomics (tumor biology) alone and is predictive of who will and who will
not benefit from chemotherapy
86
Flipits et al. Clin Cancer Res. 2011; Martin et al. Breast Cancer Res. 2014; Buus et al. J Natl Cancer Inst. 2016.
87. Risk Stratification by Oncotype DX Breast Recurrence Score® and
EndoPredict® in the Same Patient Cohorts
Assay Concordance
87
88. EndoPredict® EPclin Score and the Oncotype DX Breast Recurrence
Score® Test Do Not Identify the Same Patients as Low and High Risk
Moderate Correlation Between Assays (r = 0.45)
Varga et al. PLoS One. 2013.
N = 19 N = 15
Potential For Overtreatment:
Nearly half (47% or 7/15) of
patients identified as “high-
risk” by EPclin are “low-
risk” by Oncotype DX (RS 0-
25) and would receive no
benefit from chemotherapyN=15
N=10
N=9
Potential for Undertreatment:
21% (4/19) of patients identified
as “low-risk” by EPclin are
“high-risk” by Oncotype DX (RS
26-100) and would not receive
chemotherapy
RS: Recurrence Score
EPclin: EndoPredict molecular score + tumor size + nodal status
88
89. EndoPredict® Consistently Classifies 35%-52% of ER-Positive, HER2-
Negative Postmenopausal Patients as “High Risk” in Multiple Studies
These results are not consistent with known biology of ER-positive, HER2-negative breast cancer
EndoPredict does not have chemotherapy prediction data, resulting in potential overtreatment with
chemotherapy in many of the patients that are identified as high risk
ER: estrogen receptor
HER2: human epidermal growth factor receptor 2
89
Varga et al. PLoS One. 2013.; Buus et al. J Natl Cancer Inst. 2016.; Filipits et al. Clin Cancer Res. 2011.
EPclin Risk Score
Varga Study
44%
High risk
ABCSG6
52%
High risk
ABCSG8
35%
High risk
TransATAC
41%
High risk
91. Genomic Assays for Breast Cancer Are NOT the Same
Commercially Available Tests Are Not Interchangeable
1. Paik et al. N Engl J Med. 2004.; 2. Paik et al. J Clin Oncol. 2006.; 3. Dowsett et al. J Clin Oncol. 2013.; 4. Gnant et al. Ann Oncol. 2013.
Oncotype DX® (21-gene assay) Prosigna® (58-gene assay)
Quantitative gene expression by RT-PCR
Nanostring nCounter® – intrinsic subtyping and
gene expression
Recurrence Score® Result – calculated from gene
expression only in central laboratory
Risk of Recurrence (ROR) Score – correlates tumor
gene expression with PAM50 molecular profiles plus
tumor size in local pathology laboratory
Prospectively validated for prognosis Validated for prognosis (no prospective data)
Validated for predicting therapy benefit:
- Lack of chemotherapy benefit (RS 0-25)
- Significant chemotherapy benefit (RS 26-100)
- Endocrine therapy benefit based on quantitative ESR1
expression (ER)
No evidence for chemotherapy or endocrine therapy
prediction
Results provide:
Prognosis: Continuous score provides
individualized risk of recurrence
Prediction: Largely binary result for chemotherapy
prediction
Results provide:
Prognosis*: Continuous score provides
individualized risk of recurrence; risk groups for node-
negative (L/I/H) and node-positive (L/H)
Prediction: None
91
92. Prognosis with Prosigna® Risk of Recurrence (ROR) Score
Combines Intrinsic Subtyping with Gene Expression and Tumor Size
Patient’s tumor gene expression profile is
compared to PAM50 molecular profiles
(centroids) to determine degree of correlation
Dowsett et al. J Clin Oncol. 2013.; Gnant et al. Ann Oncol. 2013.
Correlation to PAM50 profile is combined
with proliferation score and tumor size to
generate an ROR Score
92
93. Prosigna® Studies Prove That the Risk of Recurrence (ROR) Score is
Prognostic Only and Have NOT Shown to be Predictive of
Chemotherapy Benefit
Study Treatment
Pre-
menopausal
Post-
menopausal
ER+ ER- LN+ LN- Prognostic
Chemo
Prediction
Jensen. Breast Cancer Res.
2018 (n = 460)
C, CMF, or
untreated
X X X X X Yes No
Liu. npj Breast Cancer. 2016
(n = 1311)
ACT X X X X X Yes No
Liu. Breast Cancer Res Treat.
2015 (n = 1094)
CEF, AC/T or
EC/T
X X X X X X No No
Gnant. Annals of Oncol. 2014
(n = 1478)
TAM or
TAM/AI
X X X X Yes N/A
Dowsett. J Clin Oncol. 2013
(n = 1017)
TAM or AI X X X X Yes N/A
l
ER: estrogen receptor
LN: lymph node
CMF: cyclophosphamide, methotrexate, fluorouracil
ACT: doxorubicin, cyclophosphamide, paclitaxel
CEF: cyclophosphamide, epirubicin, flurouracil
ECT: epirubicin, cyclophosphamide, paclitaxel
TAM: tamoxifen
AI: aromatase inhibitor
93
94. MA.21 Clinical Validation: Prosigna® Risk of Recurrence (ROR) Score
Is Neither Prognostic Nor Predictive of Chemotherapy Benefit
Liu et al. Breast Cancer Res Treat. 2015.
MA.21 Study
Luminal B vs A:
HR 1.20, 95% CI
0.90-1.80;
P = 0.37
In the MA.21 study, ROR Score and Luminal A/B subtypes were neither
prognostic nor predictive of chemotherapy benefit
(Interaction P = 0.23)
ROR
94
95. TransATAC: Prognostic Comparison of Prosigna® Risk of
Recurrence Score and Oncotype DX Breast Recurrence Score®
• Rate of distant recurrence is comparable between ROR and RS risk groups
• When compared by C Index, both scores are prognostic with the addition of the same clinical/pathologic
prognostic parameters (CTS = nodal status, tumor size, grade, age, AI/TAM treatment)
Dowsett et al. J Clin Oncol. 2013.
(< 10% risk)
gene expression + tumor size
gene expression only
gene expression + clin/path
(10%-20% risk)
(> 20% risk)
(10%-20% risk)
(> 20% risk)
(< 10% risk)
ROR: Risk of Recurrence Score
RS: Recurrence Score result
CTS: clinical treatment score
HER2: human epidermal growth factor receptor 2
95
96. Prosigna® Risk of Recurrence (ROR) Score and Intrinsic Subtypes in
Premenopausal Patients Randomized to No Treatment or
Chemotherapy (N = 460)
Jensen et al. Breast Cancer Res. 2018.
Disease-Free Survival (DFS)
Though continuous ROR score was prognostic in
untreated patients (DFS, P <0.001), there was no
statistically significant interaction between ROR risk
groups and chemotherapy treatment
Prosigna ROR Score and Luminal A/B subtypes are not predictive of
chemotherapy benefit in ER-positive/HER2-negative patients
A significant interaction was observed between
intrinsic subtypes and chemotherapy treatment for
DFS (Pinteraction = 0.003), due to a pronounced effect
in basal-like subtype, not ER+/HER2-negative
DFS: disease-free survival
ER: estrogen receptor
HER2: human epidermal growth factor receptor 2
96
97. Does Prosigna® Risk of Recurrence (ROR) Provide Clarity on
Adjuvant Therapy Decisions?
• Relies on pathologic features to improve its prognostic value
• Validated in heterogeneous patient populations
• No prospective data
• Not shown to be predictive of chemotherapy benefit
In N0 and N1 patients, Oncotype DX Breast Recurrence Score® test is
highly prognostic based on genomics (tumor biology) alone and
predictive of who will and who will not benefit from chemotherapy
97
Jensen et al. Breast Cancer Res. 2018.; Liu et al. npj Breast Cancer. 2016.; Liu et al. Breast Cancer Res Treat. 2015.; Gnant et al. Annals of Oncol. 2013.; Dowett et al. J Clin Oncol. 2013.
98. Risk Stratification by Oncotype DX Breast Recurrence Score® and Prosigna®
in the Same Patient Cohorts
Assay Concordance
98
99. Poor Correlation: The Oncotype DX Breast Recurrence Score® and
Prosigna® Results in Node-Negative Patients
Correlation Between Tests Is Poor (Spearman 0.08)
Alvarado et al. Adv Ther. 2015.
Of the node-negative patient samples classified as high risk by Prosigna, 57% (4/7 samples)
had low Recurrence Score® results and would be overtreated with chemotherapy
Recurrence Score = 25
99
100. Multiple Studies Consistently Show Prosigna® Risk of Recurrence
(ROR) Score Classifies >26% of ER-Positive, HER2-Negative
Patients as “High Risk”
Dowsett et al. J Clin Oncol. 2013.; Filipits et al. Clin Cancer Res. 2014.; Lænkholm et al. J Clin Oncol. 2018.
TransATAC
26%
High risk
ABCSG8
34%
High risk
Danish Registry
42%
High risk
The Prosigna ROR Score has been proven NOT to be predictive of chemotherapy benefit
and overclassifies patients as high risk, resulting in overtreatment with chemotherapy
100
101. Trial Assigning IndividuaLized Options
for TReatment (TAILORx)
Phase 3 trial of chemoendocrine therapy versus endocrine therapy alone in
HR-positive, HER2-negative, node-negative breast cancer and an
intermediate prognosis 21-gene Recurrence Score®
101
103. Prospective Validation of the Breast Recurrence Score® Test in TAILORx
Provides the Highest Level of Evidence for Adjuvant Treatment Decisions
• The TAILORx study utilized the Oncotype DX Breast Recurrence Score® (RS) test to
definitively prove that HR-positive, HER2-negative, node-negative patients with RS
results 0-25 do not benefit from chemotherapy
• Safely spares patients with RS results 0-25 from overtreatment, as they have excellent outcomes with
endocrine therapy alone
• Provides information on potential chemotherapy benefit for patients ≤50 years with
RS results 16-25
• Prognostic subgroups studied in TAILORx (ie, tumor size, tumor grade) do NOT predict
who will or will not benefit from chemotherapy
• Consistent findings with NSABP B-20 confirm recommendations for adjuvant
chemotherapy for patients with RS results 26-100 eliminating risk for undertreatment
103
Paik et al. J Clin Oncol. 2006.; Sparano et al. J Clin Oncol. 2008.; Sparano et al. N Engl J Med. 2018.