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.
From Alzahra Oncology Center in Dubai, in the heart of Middle East lead by Dr Sadir Alrawi AMERICAN boarded, minimal invasive surgery, with Dr Thamir Alkasab, Khaled Koutech and Dr Ziad Aluobiadi
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.
Pruebas genómicas de recurrencia en cáncer de mama - OncotypeDx y su entornoMauricio Lema
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
1. Resection offers the only chance of cure for pancreatic cancer, but adjuvant therapy after surgery may improve outcomes. Studies have shown benefits from chemoradiation over chemotherapy alone.
2. For borderline resectable or locally advanced unresectable disease, neoadjuvant therapy or chemoradiation may help make initially unresectable tumors operable or improve survival compared to chemotherapy alone.
3. Intensity modulated radiation therapy (IMRT) allows safer dose escalation and better sparing of nearby organs compared to 3D conformal radiation, potentially improving local control and survival. Proper motion management and image guidance are needed to fully realize the benefits of IMRT.
This document discusses various treatment options for prostate cancer based on risk level. For low risk prostate cancer with a life expectancy under 10 years, observation is recommended. For intermediate risk prostate cancer, options include radiation therapy with a short course of hormone therapy or surgery with radiation and hormone therapy if high risk features are present. For high risk prostate cancer, initial treatment involves radiation therapy with a long course of hormone therapy or surgery with radiation and long course hormone therapy if high risk features or positive lymph nodes are present. Very high risk prostate cancer may be treated with hormone therapy alone or similarly to metastatic disease.
This document summarizes recent advances in treating triple negative breast cancer (TNBC). TNBC accounts for 15-20% of breast cancers and has a poorer prognosis than other subtypes. New classifications identify basal-like and other subtypes. Standard chemotherapy remains the first-line treatment for early and advanced TNBC, but adding platinum agents or nab-paclitaxel to neoadjuvant chemotherapy improves outcomes. PARP inhibitors such as olaparib and talazoparib improve progression-free survival in BRCA-mutated metastatic TNBC. Immunotherapy with atezolizumab, pembrolizumab or combinations improves progression-free and overall survival in PD-L1 positive advanced
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.
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
From Alzahra Oncology Center in Dubai, in the heart of Middle East lead by Dr Sadir Alrawi AMERICAN boarded, minimal invasive surgery, with Dr Thamir Alkasab, Khaled Koutech and Dr Ziad Aluobiadi
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.
Pruebas genómicas de recurrencia en cáncer de mama - OncotypeDx y su entornoMauricio Lema
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
1. Resection offers the only chance of cure for pancreatic cancer, but adjuvant therapy after surgery may improve outcomes. Studies have shown benefits from chemoradiation over chemotherapy alone.
2. For borderline resectable or locally advanced unresectable disease, neoadjuvant therapy or chemoradiation may help make initially unresectable tumors operable or improve survival compared to chemotherapy alone.
3. Intensity modulated radiation therapy (IMRT) allows safer dose escalation and better sparing of nearby organs compared to 3D conformal radiation, potentially improving local control and survival. Proper motion management and image guidance are needed to fully realize the benefits of IMRT.
This document discusses various treatment options for prostate cancer based on risk level. For low risk prostate cancer with a life expectancy under 10 years, observation is recommended. For intermediate risk prostate cancer, options include radiation therapy with a short course of hormone therapy or surgery with radiation and hormone therapy if high risk features are present. For high risk prostate cancer, initial treatment involves radiation therapy with a long course of hormone therapy or surgery with radiation and long course hormone therapy if high risk features or positive lymph nodes are present. Very high risk prostate cancer may be treated with hormone therapy alone or similarly to metastatic disease.
This document summarizes recent advances in treating triple negative breast cancer (TNBC). TNBC accounts for 15-20% of breast cancers and has a poorer prognosis than other subtypes. New classifications identify basal-like and other subtypes. Standard chemotherapy remains the first-line treatment for early and advanced TNBC, but adding platinum agents or nab-paclitaxel to neoadjuvant chemotherapy improves outcomes. PARP inhibitors such as olaparib and talazoparib improve progression-free survival in BRCA-mutated metastatic TNBC. Immunotherapy with atezolizumab, pembrolizumab or combinations improves progression-free and overall survival in PD-L1 positive advanced
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.
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
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
Uterine Cancer Recurrence: All You Need To Knowbkling
t's not uncommon for uterine cancer survivors to worry about recurrence.
Whether you've had a recurrence or want to become more informed, join Dr. Susan C. Modesitt, Director of Gynecologic Oncology at UVA Cancer Center, to learn more information about uterine cancer recurrence as well as available treatment options.
Optimizing the Management of Metastatic TNBC: Diagnostics, Treatments and Hop...bkling
The treatment for mTNBC is evolving with the identification of biomarkers and clinical trials revealing new treatment options. Join us to hear from our expert guests, Dr. Paolo Tarantino, an advanced research fellow at Dana-Farber Cancer Institute and at Harvard Medical School, and Dr. Ana Garrido-Castro, Breast Medical Oncologist at Dana-Farber Cancer Institute (DFCI) and Assistant Professor of Medicine at Harvard Medical School.They will present the important changes in genetic/ biomarker diagnostics, immunotherapy as well as emerging therapies. This presentation will also highlight racial disparities and how TNBC disproportionately affects the Black community. Register now and discover your clinical options. Feel free to bring any questions you may have for discussion after the presentation.
This document summarizes management strategies for metastatic hormone receptor positive breast cancer. It discusses that hormone receptor positive disease has better survival rates than other subtypes. Roughly 30% of early breast cancer patients will develop advanced or metastatic disease, with 6-10% presenting with metastases initially. Treatment modalities discussed include reducing estrogen production, selective estrogen receptor modulators like tamoxifen, aromatase inhibitors, fulvestrant, progestins, targeted therapies, CDK4/6 inhibitors, PI3K/AKT/mTOR pathway inhibitors, and mTOR inhibitors. Combination treatment strategies are also summarized.
Olaparib in Metastatic Pancreatic Cancer Chandan K Das
The POLO trial was a randomized, double-blind, placebo-controlled study that evaluated olaparib maintenance therapy in patients with gBRCAm metastatic pancreatic cancer who had not progressed after first-line platinum-based chemotherapy. The study enrolled 154 patients from 12 countries between 2015-2019. The primary endpoint was progression-free survival assessed by blinded independent central review. Key results showed a statistically significant improvement in progression-free survival in the olaparib arm compared to placebo.
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.
The best way to treat locally advanced rectal cancerMohamed Abdulla
This document discusses treatment approaches for locally advanced rectal cancer. It begins with basic facts about colorectal cancer incidence and risk factors. It then outlines the principles of surgery as the cornerstone treatment but notes the high rates of local recurrence without adjuvant radiation therapy. The document reviews evidence demonstrating the benefits of total mesorectal excision surgery and chemoradiation in reducing recurrence rates. It examines neoadjuvant and adjuvant chemotherapy approaches, noting some trials found no benefit to adjuvant therapy especially for those who received preoperative chemoradiation. The document discusses moving towards a total neoadjuvant paradigm with upfront chemotherapy and chemoradiation to achieve pathologic complete responses when possible.
Total neoadjuvant therapy (TNT) involves administering all preoperative therapies (chemotherapy and radiotherapy) before surgery for locally advanced rectal cancer. Several studies have shown TNT results in higher pathologic complete response rates compared to standard preoperative chemoradiotherapy. The PRODIGE 23 trial found TNT resulted in significantly higher 3-year disease-free and overall survival rates as well. However, long-term data is still needed to determine if TNT can improve overall survival compared to standard treatment. While TNT shows promise, further research is still needed to identify which patients benefit most from this intensive approach.
This document summarizes the management of carcinoma of the oesophagus. It discusses the AJCC TNM classification and staging for squamous cell carcinoma and adenocarcinoma. It also describes surgical options like esophagectomy and conservative procedures. Non-surgical treatments including chemotherapy regimens, radiotherapy alone or with chemotherapy are mentioned. Several studies evaluating the role of neoadjuvant chemoradiotherapy and chemotherapy prior to surgery are summarized. Meta-analyses demonstrating improved survival with neoadjuvant therapy are also highlighted.
This document discusses chemotherapy for gliomas. It begins by covering early trials of carmustine for glioblastoma in the 1960s. It then summarizes the landmark 2005 Stupp trial which showed improved survival with temozolomide combined with radiation therapy for newly diagnosed glioblastoma. The document also discusses trials of bevacizumab and other targeted therapies as well as immunotherapy approaches. It reviews treatment options for recurrent glioblastoma and anaplastic glioma. Finally, it briefly discusses chemotherapy approaches and trials for low-grade gliomas in both adults and children.
The document summarizes information about lung cancer, including:
1) Lung cancer subtypes are small cell carcinoma (13%), large cell carcinoma (5%), adenocarcinoma (38.3%), and squamous cell carcinoma (19.7%).
2) Adjuvant chemotherapy in resected early-stage non-small cell lung cancer (NSCC) improves survival compared to surgery alone, though benefits vary by stage. Platinum-based regimens like cisplatin and vinorelbine are commonly used.
3) For locally advanced unresectable NSCLC, concurrent chemoradiotherapy is superior to sequential chemotherapy and radiotherapy, improving median and 5-year survival.
This document discusses treatment options for a 55-year-old postmenopausal woman with newly diagnosed, hormone receptor-positive, HER2-negative metastatic breast cancer. Based on evidence from clinical trials, fulvestrant alone or in combination with a CDK 4/6 inhibitor plus an aromatase inhibitor are both recommended first-line treatment options. Fulvestrant has shown superior progression-free survival compared to anastrozole alone in the first-line setting. Adding a CDK 4/6 inhibitor to endocrine therapy further improves progression-free survival and response rates and is now considered a standard first-line treatment option for this patient population.
This document contains a checklist for evaluating stereotactic body radiation therapy (SBRT) plans for treating liver lesions, including hepatocellular carcinoma and metastases. It lists patient information, treatment details, dosimetry requirements for the tumor and normal liver tissue, and constraints for nearby organs at risk. Acceptable dose limits are provided for the maximum and minimum doses to the tumor targets and several critical structures to ensure the plan meets protocol standards for safe and effective SBRT treatment.
The document summarizes several presentations from the 2016 ASCO Annual Meeting related to breast cancer research:
1) The MA.17R study found that extending aromatase inhibitor therapy beyond 5 years reduced breast cancer recurrences by 34% compared to 5 years of treatment alone. No worsening of quality of life or new toxicities were observed.
2) The PALOMA-2 study showed that adding palbociclib to letrozole significantly prolonged progression-free survival compared to letrozole alone in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer.
3) Results from the MONARCH 1 study found that abemaciclib, a
This document discusses total neoadjuvant therapy (TNT) for rectal cancer. It summarizes evidence from trials showing that TNT with chemotherapy prior to chemoradiation and surgery improves pathologic complete response rates and reduces distant metastases compared to adjuvant chemotherapy. The document also reviews the experience with TNT at the author's institution, including a clinical complete response rate of 36% and a pathologic complete response rate of 15.6% among surgery patients. Non-operative management strategies with a watch-and-wait approach are also discussed.
The document discusses organ preservation using radiation therapy techniques like brachytherapy. It provides examples of various cancers where brachytherapy can be used to preserve organs like penis, breast, bone, soft tissue sarcomas, anal canal, tongue and others. Brachytherapy provides conformal dose distribution allowing dose escalation to tumor and sparing of adjacent normal tissues, thus helping organ preservation and improved quality of life for patients. Expertise is required for brachytherapy planning and procedures to achieve optimal outcomes of local tumor control and organ preservation.
This document summarizes current dilemmas in early management of castration-resistant prostate cancer (CRPC). It discusses definitions of CRPC and its natural history progression. Factors contributing to inevitable disease progression despite androgen deprivation therapy include alternate androgen biosynthesis, androgen receptor abnormalities, proliferation cascades, and changes in histology. Genetic alterations in prostate cancer like BRCA mutations are also reviewed. Recent positive clinical trial results establishing new standards of care for both chemo-naïve and post-docetaxel CRPC are highlighted. Optimal sequencing of available therapies remains an area of ongoing research due to heterogeneity in patient populations and lack of head-to-head trials.
Landmark chemotherapy trials in advanced ovarian cancer established platinum-based combinations as the standard of care. GOG 47 (1986) showed cisplatin improves response rates and progression-free survival compared to cyclophosphamide alone. GOG 111 (1996) found the combination of paclitaxel and cisplatin improved progression-free and overall survival over cyclophosphamide and cisplatin. Subsequent trials determined carboplatin as an effective alternative to cisplatin, with fewer side effects.
Metronomic chemotherapy involves administering lower doses of chemotherapy drugs more frequently to target tumor growth. This summary approach has three potential mechanisms of action - inhibiting angiogenesis, stimulating the immune system, and directly targeting tumor cells. It yields long-term improved outcomes despite slower initial decreases in tumor size compared to maximum tolerated dose regimens. Clinical trials have shown metronomic chemotherapy to be an effective treatment approach in several cancer types including breast, colon, ovarian and prostate cancer when used as a single agent or in combinations.
Metastatic breast cancer, specifically HER2-positive subtype, represents an advanced stage of breast cancer characterized by the presence of human epidermal growth factor receptor 2 (HER2) overexpression. HER2-positive breast cancer tends to be more aggressive, but advancements in treatment options have significantly improved outcomes.
Targeted therapies play a crucial role in managing metastatic HER2-positive breast cancer. Trastuzumab (Herceptin) and pertuzumab are monoclonal antibodies that specifically target the HER2 protein, inhibiting its activity and impeding cancer cell growth. These drugs are often used in combination with chemotherapy to enhance their effectiveness.
In addition to trastuzumab and pertuzumab, other HER2-targeted therapies such as ado-trastuzumab emtansine (Kadcyla) and lapatinib may be employed in certain cases. Ado-trastuzumab emtansine is an antibody-drug conjugate that delivers chemotherapy directly to HER2-positive cancer cells, minimizing damage to healthy cells. Lapatinib, on the other hand, is a small molecule inhibitor that blocks HER2 and other related receptors.
Given the chronic nature of metastatic breast cancer, treatment plans are often individualized based on the patient's overall health, specific characteristics of the cancer, and prior treatments. Hormone therapy may also be considered if the cancer is hormone receptor-positive. Clinical trials and ongoing research continue to explore novel treatment options, providing hope for further advancements in managing HER2-positive metastatic breast cancer. Patients are encouraged to work closely with their healthcare team to determine the most appropriate and effective treatment plan tailored to their unique circumstances.
- HER2-positive early-stage breast cancer can be treated with neoadjuvant chemotherapy to shrink tumors and increase the rate of breast conservation.
- The addition of trastuzumab to neoadjuvant chemotherapy significantly increases pathological complete response (pCR) rates. Achieving pCR correlates with improved long-term outcomes.
- Adding pertuzumab to trastuzumab and chemotherapy further increases pCR rates compared to chemotherapy and trastuzumab alone. Trials also suggest improved long-term outcomes with dual anti-HER2 blockade.
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
Uterine Cancer Recurrence: All You Need To Knowbkling
t's not uncommon for uterine cancer survivors to worry about recurrence.
Whether you've had a recurrence or want to become more informed, join Dr. Susan C. Modesitt, Director of Gynecologic Oncology at UVA Cancer Center, to learn more information about uterine cancer recurrence as well as available treatment options.
Optimizing the Management of Metastatic TNBC: Diagnostics, Treatments and Hop...bkling
The treatment for mTNBC is evolving with the identification of biomarkers and clinical trials revealing new treatment options. Join us to hear from our expert guests, Dr. Paolo Tarantino, an advanced research fellow at Dana-Farber Cancer Institute and at Harvard Medical School, and Dr. Ana Garrido-Castro, Breast Medical Oncologist at Dana-Farber Cancer Institute (DFCI) and Assistant Professor of Medicine at Harvard Medical School.They will present the important changes in genetic/ biomarker diagnostics, immunotherapy as well as emerging therapies. This presentation will also highlight racial disparities and how TNBC disproportionately affects the Black community. Register now and discover your clinical options. Feel free to bring any questions you may have for discussion after the presentation.
This document summarizes management strategies for metastatic hormone receptor positive breast cancer. It discusses that hormone receptor positive disease has better survival rates than other subtypes. Roughly 30% of early breast cancer patients will develop advanced or metastatic disease, with 6-10% presenting with metastases initially. Treatment modalities discussed include reducing estrogen production, selective estrogen receptor modulators like tamoxifen, aromatase inhibitors, fulvestrant, progestins, targeted therapies, CDK4/6 inhibitors, PI3K/AKT/mTOR pathway inhibitors, and mTOR inhibitors. Combination treatment strategies are also summarized.
Olaparib in Metastatic Pancreatic Cancer Chandan K Das
The POLO trial was a randomized, double-blind, placebo-controlled study that evaluated olaparib maintenance therapy in patients with gBRCAm metastatic pancreatic cancer who had not progressed after first-line platinum-based chemotherapy. The study enrolled 154 patients from 12 countries between 2015-2019. The primary endpoint was progression-free survival assessed by blinded independent central review. Key results showed a statistically significant improvement in progression-free survival in the olaparib arm compared to placebo.
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.
The best way to treat locally advanced rectal cancerMohamed Abdulla
This document discusses treatment approaches for locally advanced rectal cancer. It begins with basic facts about colorectal cancer incidence and risk factors. It then outlines the principles of surgery as the cornerstone treatment but notes the high rates of local recurrence without adjuvant radiation therapy. The document reviews evidence demonstrating the benefits of total mesorectal excision surgery and chemoradiation in reducing recurrence rates. It examines neoadjuvant and adjuvant chemotherapy approaches, noting some trials found no benefit to adjuvant therapy especially for those who received preoperative chemoradiation. The document discusses moving towards a total neoadjuvant paradigm with upfront chemotherapy and chemoradiation to achieve pathologic complete responses when possible.
Total neoadjuvant therapy (TNT) involves administering all preoperative therapies (chemotherapy and radiotherapy) before surgery for locally advanced rectal cancer. Several studies have shown TNT results in higher pathologic complete response rates compared to standard preoperative chemoradiotherapy. The PRODIGE 23 trial found TNT resulted in significantly higher 3-year disease-free and overall survival rates as well. However, long-term data is still needed to determine if TNT can improve overall survival compared to standard treatment. While TNT shows promise, further research is still needed to identify which patients benefit most from this intensive approach.
This document summarizes the management of carcinoma of the oesophagus. It discusses the AJCC TNM classification and staging for squamous cell carcinoma and adenocarcinoma. It also describes surgical options like esophagectomy and conservative procedures. Non-surgical treatments including chemotherapy regimens, radiotherapy alone or with chemotherapy are mentioned. Several studies evaluating the role of neoadjuvant chemoradiotherapy and chemotherapy prior to surgery are summarized. Meta-analyses demonstrating improved survival with neoadjuvant therapy are also highlighted.
This document discusses chemotherapy for gliomas. It begins by covering early trials of carmustine for glioblastoma in the 1960s. It then summarizes the landmark 2005 Stupp trial which showed improved survival with temozolomide combined with radiation therapy for newly diagnosed glioblastoma. The document also discusses trials of bevacizumab and other targeted therapies as well as immunotherapy approaches. It reviews treatment options for recurrent glioblastoma and anaplastic glioma. Finally, it briefly discusses chemotherapy approaches and trials for low-grade gliomas in both adults and children.
The document summarizes information about lung cancer, including:
1) Lung cancer subtypes are small cell carcinoma (13%), large cell carcinoma (5%), adenocarcinoma (38.3%), and squamous cell carcinoma (19.7%).
2) Adjuvant chemotherapy in resected early-stage non-small cell lung cancer (NSCC) improves survival compared to surgery alone, though benefits vary by stage. Platinum-based regimens like cisplatin and vinorelbine are commonly used.
3) For locally advanced unresectable NSCLC, concurrent chemoradiotherapy is superior to sequential chemotherapy and radiotherapy, improving median and 5-year survival.
This document discusses treatment options for a 55-year-old postmenopausal woman with newly diagnosed, hormone receptor-positive, HER2-negative metastatic breast cancer. Based on evidence from clinical trials, fulvestrant alone or in combination with a CDK 4/6 inhibitor plus an aromatase inhibitor are both recommended first-line treatment options. Fulvestrant has shown superior progression-free survival compared to anastrozole alone in the first-line setting. Adding a CDK 4/6 inhibitor to endocrine therapy further improves progression-free survival and response rates and is now considered a standard first-line treatment option for this patient population.
This document contains a checklist for evaluating stereotactic body radiation therapy (SBRT) plans for treating liver lesions, including hepatocellular carcinoma and metastases. It lists patient information, treatment details, dosimetry requirements for the tumor and normal liver tissue, and constraints for nearby organs at risk. Acceptable dose limits are provided for the maximum and minimum doses to the tumor targets and several critical structures to ensure the plan meets protocol standards for safe and effective SBRT treatment.
The document summarizes several presentations from the 2016 ASCO Annual Meeting related to breast cancer research:
1) The MA.17R study found that extending aromatase inhibitor therapy beyond 5 years reduced breast cancer recurrences by 34% compared to 5 years of treatment alone. No worsening of quality of life or new toxicities were observed.
2) The PALOMA-2 study showed that adding palbociclib to letrozole significantly prolonged progression-free survival compared to letrozole alone in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer.
3) Results from the MONARCH 1 study found that abemaciclib, a
This document discusses total neoadjuvant therapy (TNT) for rectal cancer. It summarizes evidence from trials showing that TNT with chemotherapy prior to chemoradiation and surgery improves pathologic complete response rates and reduces distant metastases compared to adjuvant chemotherapy. The document also reviews the experience with TNT at the author's institution, including a clinical complete response rate of 36% and a pathologic complete response rate of 15.6% among surgery patients. Non-operative management strategies with a watch-and-wait approach are also discussed.
The document discusses organ preservation using radiation therapy techniques like brachytherapy. It provides examples of various cancers where brachytherapy can be used to preserve organs like penis, breast, bone, soft tissue sarcomas, anal canal, tongue and others. Brachytherapy provides conformal dose distribution allowing dose escalation to tumor and sparing of adjacent normal tissues, thus helping organ preservation and improved quality of life for patients. Expertise is required for brachytherapy planning and procedures to achieve optimal outcomes of local tumor control and organ preservation.
This document summarizes current dilemmas in early management of castration-resistant prostate cancer (CRPC). It discusses definitions of CRPC and its natural history progression. Factors contributing to inevitable disease progression despite androgen deprivation therapy include alternate androgen biosynthesis, androgen receptor abnormalities, proliferation cascades, and changes in histology. Genetic alterations in prostate cancer like BRCA mutations are also reviewed. Recent positive clinical trial results establishing new standards of care for both chemo-naïve and post-docetaxel CRPC are highlighted. Optimal sequencing of available therapies remains an area of ongoing research due to heterogeneity in patient populations and lack of head-to-head trials.
Landmark chemotherapy trials in advanced ovarian cancer established platinum-based combinations as the standard of care. GOG 47 (1986) showed cisplatin improves response rates and progression-free survival compared to cyclophosphamide alone. GOG 111 (1996) found the combination of paclitaxel and cisplatin improved progression-free and overall survival over cyclophosphamide and cisplatin. Subsequent trials determined carboplatin as an effective alternative to cisplatin, with fewer side effects.
Metronomic chemotherapy involves administering lower doses of chemotherapy drugs more frequently to target tumor growth. This summary approach has three potential mechanisms of action - inhibiting angiogenesis, stimulating the immune system, and directly targeting tumor cells. It yields long-term improved outcomes despite slower initial decreases in tumor size compared to maximum tolerated dose regimens. Clinical trials have shown metronomic chemotherapy to be an effective treatment approach in several cancer types including breast, colon, ovarian and prostate cancer when used as a single agent or in combinations.
Metastatic breast cancer, specifically HER2-positive subtype, represents an advanced stage of breast cancer characterized by the presence of human epidermal growth factor receptor 2 (HER2) overexpression. HER2-positive breast cancer tends to be more aggressive, but advancements in treatment options have significantly improved outcomes.
Targeted therapies play a crucial role in managing metastatic HER2-positive breast cancer. Trastuzumab (Herceptin) and pertuzumab are monoclonal antibodies that specifically target the HER2 protein, inhibiting its activity and impeding cancer cell growth. These drugs are often used in combination with chemotherapy to enhance their effectiveness.
In addition to trastuzumab and pertuzumab, other HER2-targeted therapies such as ado-trastuzumab emtansine (Kadcyla) and lapatinib may be employed in certain cases. Ado-trastuzumab emtansine is an antibody-drug conjugate that delivers chemotherapy directly to HER2-positive cancer cells, minimizing damage to healthy cells. Lapatinib, on the other hand, is a small molecule inhibitor that blocks HER2 and other related receptors.
Given the chronic nature of metastatic breast cancer, treatment plans are often individualized based on the patient's overall health, specific characteristics of the cancer, and prior treatments. Hormone therapy may also be considered if the cancer is hormone receptor-positive. Clinical trials and ongoing research continue to explore novel treatment options, providing hope for further advancements in managing HER2-positive metastatic breast cancer. Patients are encouraged to work closely with their healthcare team to determine the most appropriate and effective treatment plan tailored to their unique circumstances.
- HER2-positive early-stage breast cancer can be treated with neoadjuvant chemotherapy to shrink tumors and increase the rate of breast conservation.
- The addition of trastuzumab to neoadjuvant chemotherapy significantly increases pathological complete response (pCR) rates. Achieving pCR correlates with improved long-term outcomes.
- Adding pertuzumab to trastuzumab and chemotherapy further increases pCR rates compared to chemotherapy and trastuzumab alone. Trials also suggest improved long-term outcomes with dual anti-HER2 blockade.
Clinical challenges in management of her 2 positive by gladwell kiarieKesho Conference
This document summarizes cancer incidence rates and management strategies for two breast cancer cases in Kenya. For case 1, a 68-year-old woman presented with nipple symptoms and imaging findings suspicious for breast cancer. A biopsy confirmed Paget's disease, DCIS, and invasive ductal carcinoma. The tumor was ER-, PR-, HER2+ and treatment with mastectomy, radiation, and HER2-targeted therapy was discussed. For case 2, a 36-year-old pregnant woman presented with a breast lump and axillary nodes concerning for cancer. Biopsy confirmed HER2+ cancer and treatment including lumpectomy, chemotherapy, mastectomy, radiation and HER2-targeted therapy during and after pregnancy was outlined while discussing trast
1. Head and neck cancers arise in the oral cavity, sinonasal cavity, pharynx, and larynx, with squamous cell carcinoma being the most common type.
2. Treatment depends on the stage and site of the cancer, and may involve surgery, radiation therapy, chemotherapy, or a combination.
3. For locally advanced disease, concurrent chemoradiotherapy is the standard of care, using high-dose cisplatin concurrently with radiation therapy.
This document summarizes targeted therapy for HER2-positive breast cancer, focusing on trastuzumab and lapatinib. It discusses the prevalence and clinical relevance of HER2 overexpression in breast cancer. It describes pivotal trials that established trastuzumab as an effective first-line and adjuvant therapy, and lapatinib as an option for patients progressing on trastuzumab. Mechanisms of resistance to trastuzumab are discussed along with additional anti-HER2 agents in development.
Journal club: Durvalumab as Consolidation therapy in Advanced NSCLCAnimesh Agrawal
This study evaluated the addition of durvalumab consolidation therapy following chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer. The study found that durvalumab improved progression-free survival compared to placebo, with median progression-free survival of 16.8 months versus 5.6 months respectively. Overall survival was also improved with durvalumab, though final analysis is still pending. Safety profiles were similar to other PD-L1 inhibitors, with immune-related adverse events in approximately 25% of durvalumab patients. This study provides evidence that durvalumab consolidation improves outcomes for stage III NSCLC following chemoradiotherapy.
- The document summarizes a clinical trial that compared cisplatin chemotherapy plus radiotherapy (standard treatment) to cetuximab (EGFR inhibitor) plus radiotherapy for low-risk HPV-positive oropharyngeal cancer.
- The trial found that using cetuximab instead of cisplatin resulted in no reduction in toxicity but significantly worse tumor control outcomes, including lower 2-year overall survival and higher recurrence rates.
- The results suggest that cisplatin remains the standard of care for concurrent chemotherapy with radiotherapy for HPV-positive oropharyngeal cancer and that treatment de-escalation strategies removing systemic chemotherapy need caution.
Safety and clinical activity of pembrolizumab for treatmentMarwa EL-Sayed
Pembrolizumab is a humanized monoclonal antibody that targets the PD-1 receptor. This study evaluated the safety and efficacy of pembrolizumab in 104 patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The results showed that pembrolizumab had a manageable safety profile, with 63% of patients experiencing drug-related adverse events mostly grade 1-2. Pembrolizumab also demonstrated promising anti-tumor activity with an 18% overall response rate. Progression-free survival was 13 months. This study provides evidence that pembrolizumab is a potential new treatment option for this patient population.
This study compared short-course radiotherapy to long-course chemoradiation for patients with T3 rectal cancer. It found that long-course treatment resulted in a lower risk of local tumor recurrence, though the difference was not statistically significant. Both treatments had similar rates of distant tumor recurrence and overall survival. Long-course treatment seemed to provide a greater benefit for distal tumors, with fewer local recurrences, but again the difference was not statistically significant due to the small number of distal tumors.
This document discusses treatment options for locally advanced breast cancer (LABC). It notes that LABC is a heterogeneous disease and standard primary chemotherapy includes anthracyclines and taxanes. Neoadjuvant chemotherapy is now the standard of care as it allows for breast conservation in some cases and those who achieve a pathological complete response have improved survival rates. The response to neoadjuvant therapy and molecular subtypes (e.g. triple negative, HER2-positive) can help determine the most effective adjuvant treatment strategy. Targeted therapies like trastuzumab improve outcomes for HER2-positive breast cancer when given with chemotherapy in the neoadjuvant setting.
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.
The document discusses new drug developments in subsets of breast cancer. It describes how breast cancer is being segmented into rare molecular subtypes defined by specific molecular alterations. This molecular segmentation is important for optimally developing targeted agents by enriching clinical trials for patients with the relevant molecular alteration. Several new drugs for treating specific breast cancer subtypes are mentioned, including drugs targeting HER2, angiogenesis, hormone receptors, and DNA repair pathways in triple negative breast cancer.
The document discusses new drug developments in subsets of breast cancer. It describes how breast cancer is being segmented into rare molecular subtypes defined by specific molecular alterations. This molecular segmentation is important for optimally developing targeted agents by enriching clinical trials for patients with the relevant molecular alteration. Several new drugs for treating specific breast cancer subtypes are discussed, including drugs targeting HER2, angiogenesis, hormone receptors, and DNA repair pathways in triple negative breast cancer.
There are three main subtypes of breast cancer - HER2-positive, hormone receptor-positive, and triple-negative. Understanding the differences in these subtypes has allowed oncologists to guide treatment decisions and focus clinical trials on specific targets. For HER2-positive breast cancer, major advances have been made with targeted therapies like trastuzumab, pertuzumab, lapatinib, and T-DM1 which have improved outcomes. For hormone receptor-positive disease, newer agents like everolimus that target resistance pathways are being studied. Triple-negative breast cancer remains challenging but agents like platinum drugs and PARP inhibitors show promise by exploiting DNA repair deficiencies. Continued research into new targets holds hope for improving outcomes
Professor Peter Schmid, FRCP, MD, PhD, Leisha A. Emens, MD, PhD, and Heather L. McArthur, MD, MPH, prepared useful practice aids pertaining to the role of immunotherapy in triple-negative breast cancer for this CME/MOC/CNE activity titled, "On the Cusp of the Era of Immuno-Oncology in Triple-Negative Breast Cancer: Rational Strategies to Make the Most of Immunotherapies and Other Effective Treatment Modalities Throughout the Disease Continuum." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/34aGu95. CME/MOC/CNE credit will be available until December 29, 2020.
This document discusses the management of metastatic neuroendocrine tumors (NETs). It covers grading and classification of NETs, biomarkers used to diagnose and monitor disease, and various treatment options including somatostatin analogues, targeted therapies, chemotherapy, and locoregional approaches. Key clinical trials evaluating therapies for symptom control and antitumor effects in gastrointestinal and pancreatic NETs are summarized.
Chair, Kurt A. Schalper, MD, PhD, Michael F. Press, MD, PhD, Paolo Tarantino, MD, and Zev A. Wainberg, MD, prepared useful Practice Aids pertaining to immuno-oncology biomarkers for this CME/MOC/CC activity titled “Decoding the Latest Evidence and Practical Recommendations on Biomarker Testing for New Therapeutic Options Targeting HER2, HER3, and TROP2 in Solid Tumors.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CC information, and to apply for credit, please visit us at https://bit.ly/3iQ5A6Y. CME/MOC/CC credit will be available until April 22, 2022.
(June 12, 2024) Webinar: Development of PET theranostics targeting the molecu...Scintica Instrumentation
Targeting Hsp90 and its pathogen Orthologs with Tethered Inhibitors as a Diagnostic and Therapeutic Strategy for cancer and infectious diseases with Dr. Timothy Haystead.
The technology uses reclaimed CO₂ as the dyeing medium in a closed loop process. When pressurized, CO₂ becomes supercritical (SC-CO₂). In this state CO₂ has a very high solvent power, allowing the dye to dissolve easily.
Mending Clothing to Support Sustainable Fashion_CIMaR 2024.pdfSelcen Ozturkcan
Ozturkcan, S., Berndt, A., & Angelakis, A. (2024). Mending clothing to support sustainable fashion. Presented at the 31st Annual Conference by the Consortium for International Marketing Research (CIMaR), 10-13 Jun 2024, University of Gävle, Sweden.
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
PPT on Direct Seeded Rice presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
Sexuality - Issues, Attitude and Behaviour - Applied Social Psychology - Psyc...PsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
ESA/ACT Science Coffee: Diego Blas - Gravitational wave detection with orbita...Advanced-Concepts-Team
Presentation in the Science Coffee of the Advanced Concepts Team of the European Space Agency on the 07.06.2024.
Speaker: Diego Blas (IFAE/ICREA)
Title: Gravitational wave detection with orbital motion of Moon and artificial
Abstract:
In this talk I will describe some recent ideas to find gravitational waves from supermassive black holes or of primordial origin by studying their secular effect on the orbital motion of the Moon or satellites that are laser ranged.
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
2. AGENDA
• 1.características epidemiologias HER 2 +
• 2. PERTUZUMAB características generales
• Vías moleculares cancer de mama HER2+
• 3. PERTUZUMAB EN NEOADYUVANCIA
• 4. PERTUZUMAB EN ADYUVANCIA
• 5. PERTUZUMAB EN PRIMERA LINEA
• 6. TOXICIDADES
• BERENICE
• NCCN/ESMO INDICACIONES DE PERTUZUMAB
• CASO CLINICO
• 7 CONCLUSIONES
3. • Representa aproximadamente el 15-
20 % de todos los cánceres de
mama.
• Amplificación del gen HER2
sobreexpresión de la proteína HER2.
• Comportamiento biológico agresivo
• Se asocia con una DFS más corta y
peores tasas OS que otros subtipos
de cáncer de mama.
CANCER DE MAMA SUBTIPO HER2 POSITIVO
Posibilidad única de utilizar un enfoque de tratamiento dirigido.
4. HER 2
• Receptor de TIROSINA QUINASA
perteneciente a la familia del
receptor de factor de
crecimiento epidérmico humado.
• Regulación del crecimiento
celular, la supervivencia y la
diferenciación.
La sobreexpresión de HER2 proliferación celular inhibición la apoptosis Cancer
7. ROLE IN SIGNALING PATHWAYS
UNION DE LIGANDO ESPECIFICO
HER 2 CONFORMACION ACTIVADA DE
FORMA CONSTITUTIVA
“PAREJA DE DIMERIZACION PREFERIDA”
CON LA MAS POTENTE ACTIVIDAD
KINASA.
- HER2/HER3
9. ACCION ONCOGÉNICA DE HER2
AMPLIFICACION
(Her2/neu)
SOBREEXPRESION
HETERODIMERIZA
CION
ACTIVACIÓN DE
VIAS DE
SEÑALIZACIÓN
CELULAR
CRECIMIENTO
TUMORAL Y
CANCER
10. PERTUZUMAB
Anticuerpo monoclonal humanizado.
Okines, F. C., & Cunningham, D. (2012). Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.
EVITA LA DIMERIZACION DE LOS RTK
DE LA FAMILIA HER 2
Mecanismo de acción complementario a
trastuzumab sinergismo
11. Se une al Dominio II de la
porción extracelular de HER 2
12. Pertuzumab bloquea la accion del ligando
Neuregulin 1-2 e inhibe la activación de la via
de señalización PI3k/AKT/MTOR
Estimula la citotoxicidad celular dependiente
de anticuerpos
13. Hubalek, M., Brantner, C., & Marth, C. (2011). Role of pertuzumab in the treatment of HER2-positive breast cancer. Breast Cancer : Ta
and Therapy, 4, 65-73.
14. Toxicidades
• The results of a recently published meta-analysis of 14 Phase II trials, which included 598 patients, demonstrated that pertuzumab (exposure ranging from a
median of three cycles to a median of 26 cycles) was generally well tolerated.
• The incidence of LVSD was low, with most events being asymptomatic and detected at scheduled evaluations.
• The median timing of LVSD and HF was around cycle 4 (range 1–15) with 34/39 (87%) events occurring between cycles 1 and 7. Additionally, when
pertuzumab was administered in combination with trastuzumab or nonanthracycline-containing cytotoxic chemotherapy, there was no marked increase in
observed cardiac dysfunction.
• In this analysis of 598 unique atients exposed to pertuzumab, 35 (5.9%) cases of asymptomatic LVSD and four (0.7%) cases of symptomatic HF were
reported.
• Results from the completed NEOSPHERE, TRYPHAENA, and CLEOPATRA trials also indicate a low incidence of symptomatic and asymptomatic LVSD.
• Gastrointestinal toxicities (diarrhea, nausea, vomiting, and abdominal pain) and fatigue are the most frequently reported AEs associated with single-agent
therapy. Diarrhea and rash are common events that increased with pertuzumab in combination with Chemotherapy, compared with chemotherapy alone.
• The most common AEs during dual therapy with pertuzumab and trastuzumab in metastatic breast cancer (BO17929) were diarrhea, fatigue, nausea, and
rash.18 The majority of these AEs were NCI-CTC grade 1 or 2 in everity.
• The mechanisms behind diarrhea and rash are unknown, but similar side effects are observed with other agents that cause HER1 inhibition. The most
frequently occurring AEs during neoadjuvant treatment of patients with locally advanced breast cancer, using pertuzumab and trastuzumab in combination
with chemotherapy, were alopecia, neutropenia, diarrhea, nausea, fatigue, rash, and mucosal inflammation.
• Adding pertuzumab to the trastuzumab plus docetaxel regimen did not notably affect the overall afety profile, and the tolerability of pertuzumab plus
docetaxel was also broadly comparable to the triple regimen.
• Patients receiving trastuzumab and pertuzumab without ocetaxel in the neoadjuvant setting reported notably fewer AEs across most body systems,
compared to patients who received treatments containing chemotherapy.
• Serious or severe infusion- Related symptoms have been rarely observed in patients (0,1%) receiving pertuzumab.
15.
16.
17. HER2 Y CARDIO-TOXICIDAD
• PERTUZUMAB: Anticuerpo monoclonal
humanizado (IgG 1) dirigido contra el
dominio extracelular del receptor del
HER2 neu.
• Cardiotoxicidad: Tipo II Reducción de la
contractibilidad acompañado en algunos
casos de necrosis de miocitos en pequeña
cantidad; Función ventricular se recupera
al interrumpir el tratamiento: Reversible.
Ruiz E et al, Cardio-oncología en cáncer de mama y en cáncer de próstata, 2021
Sandoo A et al, Breast cancer therapy and cardiovascular risk: focus on Trastuzumab, Vasc Health Risk Manag, 11-2015
Abbreviations: ANG II, angiotensin II; eNOS, endothelial nitric oxide synthase; HER, human epidermal
growth receptor; NO, nitric oxide; ROS, reactive oxygen species
Terapias HER2-
target
18. MECANISMOS DE CARDIOTOXICIDAD CON
TERAPIAS HER2-TARGET
Mecanismo Acción: Neuregulina es una
proteína producida por el endotelio
microvascular coronario y el endocardio.
Esta se une al receptor HER4, el cual se
heterodimeriza con el HER2, esta unión
favorece la fosforilación del ATP, el
acoplamiento mecánico al miocito, inhibe la
producción de ROS y disminuye la apoptosis.
El trastuzumab al bloquear HER2 en los
cardiomiocitos no permitirá que se dimerice
con el HER4, inhibiendo los efectos favorables
de la neuregulina.
Ruiz E et al, Cardio-oncología en cáncer de mama y en cáncer de próstata, 2021
PERTUZUMAB
19. Cardiotoxicidad con Terapias HER2-target
Kondapalli L, Cardiotoxicity: an unexpected consequence of HER2-Targeted therapies, 2016
20. J.ˇCelutkien ̇eet al, Imaging for cardio-oncology; European Journal of Heart Failure (2020)22,1504–1524
27. Objetivo primario: Evaluar el perfil de seguridad cardiaca
1. Gianni. Lancet Oncol. 2012;13:25. 2. Schneeweiss. Ann Oncol. 2013;24:2278.
pCR assessed
at surgery
PHASE II TRYPHAENA CARDIAC SAFETY STUDY: DUAL HER2 TARGETING ±
ANTHRACYCLINE TX
6 CICLOS Q3W
A=73
C=77
B=75
Chemo-naive women
with HER2+ EBC
(operable or
LA/inflammatory);
Primary tumor > 2 cm
LVEF mayor/igual 55%
Basal
(N = 225)
Objetivo secundario: pCR (ypT0/is)
FEC + HP x 3 cycles →
THP x 3 cycles
TCHP x 6 cycles
FEC x 3 cycles →
THP x 3 cycles
Adjuvant tx
to complete
1 yr of
trastuzumab
28. MEDIA DE VARIACIÓN EN LA FEVI DURANTE EL TRATAMIENTO.
La media de LVEF cayo por
debajo de la línea de base
durante el tratamiento en
todos los brazos, sin embargo,
la media de caída no fue mas
de 7%.
29. Overall, 24 patients experienced significant LVEF declines during the study. The declines were asymptomatic in 21
of these patients.
30.
31. Schneeweiss. Ann Oncol. 2013;24:2278.
FEC + HP x 3→THP x 3
(n = 73)
pCR
±
95%
CI
(%)
FEC x 3→THP x 3
(n = 75)
TCHP x 6
(n = 77)
100
80
60
40
20
0
ypT0/is and ER and PgR negative
ypT0/is and ER and/or PgR positive
46.2
79.4
48.6
65.0
50.0
83.8
A B C
57.3% 66.2
Phase II TRYPHAENA Cardiac Safety Study: Dual HER2 Targeting ± Anthracycline Tx
ypT0/is = pCR
61.6%
32. T: TRASTUZUMAB
P: PACLITAXEL
C: CARBOPLATINO
TRAIN-2 STUDY DESING
Phase 3 trial TRAIN-2: Neoadjuvant chemotherapy with or without anthracyclines
in the presence of dual HER2 blockade for HER2-positive breast cancer.
Primary endpoint: pCR in breast ypT0/is ypN0
N=219
N=219
*PTC: Paclitaxel/trastuzumab/carboplatino
†5FU/Epirrubicina/ciclofosfamida
33. Phase 3 trial TRAIN-2: Neoadjuvant chemotherapy with or without anthracyclines
in the presence of dual HER2 blockade for HER2-positive breast cancer.
67% 68%
ANTRACICLINAS
141/212 140/206
Primary endpoint: pCR in breast ypT0/is ypN0
Median follow up 19 Month
36. APHINITY: Study Design
• International, randomized, double-blind, placebo-controlled phase III trial[1,2]
• Primary endpoint: IDFS per modified STEEP definition[3] (excludes second primary non-BC as event)
• Secondary endpoints: IDFS per STEEP definition,[3] OS, distant recurrence-free survival, DFS, recurrence-free
interval, safety, cardiac safety, health-related QoL
Pts with HER2+ EBC, no prior invasive
BC or anticancer tx or radiotherapy,
node positive + any tumor size (no T0)
or node negative + tumor size > 1 cm,*
BL LVEF ≥ 55%
(N = 4805)
Pertuzumab + Trastuzumab + CT†
(n = 2400)
Placebo + Trastuzumab + CT†
(n = 2405)
10-yr follow-up
Surgery
Wk 52
Stratified by CT, nodal status, HR status,
geographic region, protocol version (A vs B)
*Or node negative + 1 of following: for tumors > 0.5, ≤ 1 cm, at least 1 histologic/nuclear grade 3; ER negative and PgR negative;
aged < 35 yrs. †Tx initiated ≤ 8 wks post surgery. Permitted CT: standard anthracycline or nonanthracycline regimens. Endocrine and/or
radiotherapy could be started at end of adjuvant CT.
37. Slide credit: clinicaloptions.com
von Minckwitz G, et al. ASCO 2017. Abstract LBA500.
APHINITY: Pt Characteristics in ITT Population
Characteristic, n (%) Pertuzumab
(n = 2400)
Placebo
(n = 2404)
Nodal status
0 positive nodes + T ≤ 1 cm
0 positive nodes + T > 1 cm
1-3 positive nodes
≥ 4 positive nodes
90 (3.8)
807 (33.6)
907 (37.8)
596 (24.8)
84 (3.5)
818 (34.0)
900 (37.4)
602 (25.0)
Adjuvant CT regimen (randomized)
Anthracycline containing
Nonanthracycline containing
1865 (77.7)
535 (22.3)
1877 (78.1)
527 (21.9)
HR status (central determination)
Negative (ER- and PgR-)
Positive (ER+ and/or PgR+)
864 (36.0)
1536 (64.0)
858 (35.7)
1546 (64.3)
Protocol version
A
Amendment B*
1828 (76.2)
572 (23.8)
1827 (76.0)
577 (24.0)
*Capped node-negative enrollment in November 2012 (recruitment started November 2011); added 1000 node-positive pts and
increased sample size to 4800 pts total.
38. APHINITY: Interim Analysis of IDFS
• Data cutoff in December 2016 after 379 IDFS
events (median f/u: 45.4 mos)
• Most first events were visceral, distant
von Minckwitz G, et al. ASCO 2017. Abstract LBA500. Reproduced with permission.
IDFS
(%)
Mos
Pertuzumab
Placebo
Stratified HR: 0.81
(95% CI: 0.66-1.00; P = .045)
Pts at Risk, n
IDFS Event, n (%) Pertuzumab
(n = 2400)
Placebo
(n = 2404)
All pts with IDFS event 171 (7.1) 210 (8.7)
First event type
Distant recurrence
Locoregional recurrence
Contralateral BC
Death
112 (4.7)
26 (1.1)
5 (0.2)
28 (1.2)
139 (5.8)
34 (1.4)
11 (0.5)
26 (1.1)
All pts with distant recurrence 119 (5.0) 145 (6.0)
First distant recurrence site
Lung/liver/pleural effusion
CNS
Other
Bone
43 (1.8)
46 (1.9)
9 (0.4)
21 (0.9)
61 (2.5)
45 (1.9)
9 (0.4)
30 (1.2)
ITT population.
100
80
60
40
20
0
0 6 12 18 24 30 36 42 48
98.6% 96.4% 94.1% 92.3%
98.8% 95.7% 93.2% 90.6%
Pertuzumab
Placebo
2400
2404
2309
2335
2275
2312
2236
2274
2199
2215
2153
2168
2101
2108
1687
1674
879
866
(Expected: 89.2%)
41. APHINITY: 6-Yr Follow-up for IDFS in ITT Population
Piccart. JCO. 2021;39:1448.
Yr From Random Assignment
IDFS
(%)
3 Yr 6 Yr
100
80
60
40
20
0 1 2 3 4 5 6
94.1%
Pertuzumab
(n = 2400)
Placebo
(n = 2404)
90.6%
87.8%
93.2%
Events, n (%)
Stratified HR (95% Cl)
Median f/u, mo
221 (9.2) 287 (11.9)
0.76 (0.64-0.91)
74.1
6 yr from randomization
Difference in event-free rate, %
(95% CI for difference)
2.8
(1.0-4.6)
Patients at Risk, n
Pertuzumab
Placebo
2400 2277 2198 2122 2055 1978 1482
2404 2312 2215 2134 2039 1967 1421
Slide credit: clinicaloptions.com
42. APHINITY: Conclusions
• Adjuvant pertuzumab + trastuzumab + CT significantly reduced risk of recurrence events vs
placebo + trastuzumab + CT in pts with HER2+ EBC
• HR: 0.81 (95% CI: 0.66-1.00; P = .045)
• Pts with node-positive or HR-negative disease had greatest IDFS benefit
• Most recurrences to distant sites (pertuzumab: 4.7%; placebo: 5.8%)
• Investigators concluded:
• No new safety signals identified with addition of pertuzumab to trastuzumab + CT
• Low incidence of cardiac events
• No difference in fatal AE rates between arms (0.8% for both)
• Increased diarrhea incidence with pertuzumab (any-grade: 71.2% vs 45.2% with placebo)
• Ongoing follow-up important to determine long-term IDFS, safety, and OS
Slide credit: clinicaloptions.com
von Minckwitz G, et al. ASCO 2017. Abstract LBA500.
43. Phase III CLEOPATRA: Trastuzumab and
Docetaxel ± Pertuzumab in HER2+ MBC
• Primary endpoint: PFS (independently assessed)
• Secondary endpoints: PFS (investigator assessed), ORR, OS, safety
Women with
previously untreated,
HER2+ locally
recurrent/metastatic
breast cancer
(N = 808)
Trastuzumab 6 mg/kg Q3W* +
Docetaxel 75-100 mg/m2 Q3W† +
Pertuzumab 420 mg Q3W‡
(n = 402)
Trastuzumab 6 mg/kg Q3W* +
Docetaxel 75-100 mg/m2 Q3W† +
Placebo Q3W
(n = 406)
Treatment until
disease progression
or unacceptable
toxicity
Stratified by geographic region
and previous (neo)adjuvant chemotherapy
*Trastuzumab 8-mg/kg loading dose. †Minimum of 6 docetaxel cycles recommended; < 6 cycles
permitted for unacceptable toxicity or PD. ‡Pertuzumab 840-mg loading dose.
Baselga J, et al. N Engl J Med. 2012;366:109-119. Slide credit: clinicaloptions.com
44. Baselga J, et al. N Engl J Med. 2012;366:109-119.
Trastuzumab and Docetaxel ± Pertuzumab in HER2+
MBC (CLEOPATRA): PFS
PFS independently assessed.
100
90
80
70
60
50
40
30
20
10
0
PFS
(%)
Mos
40
0 5 10 15 20 25 30 35
HR: 0.62 (95% CI: 0.51-0.75);
P < .001)
Pertuzumab (median: 18.5 mos)
Control (median: 12.4 mos)
Slide credit: clinicaloptions.com
45. Trastuzumab and Docetaxel ±
Pertuzumab in HER2+ MBC
(CLEOPATRA): OS
• Second interim analysis of OS (median follow-up: 30 mos)
• Significant, confirmatory, crosses stopping boundary
Swain SM, et al. Lancet Oncol. 2013;14:461-471.
OS Pmab Placebo HR
(95% CI)
P
Value
3-yr estimated OS,
%
66 50 0.66
(0.52-0.84)
.0008
Median OS, mos Not
reached
37.6 -- --
Pertuzumab, trastuzumab, docetaxel
Placebo, trastuzumab, docetaxel
100
80
60
40
20
0
OS
(%)
Mos
55
0 5 10 20 25 30 35 40 45 50
15
Slide credit: clinicaloptions.com
46. Select Adverse Events (Grade ≥ 3), %
Pertuzumab
(n = 407)
Placebo
(n = 397)
Neutropenia 48.9 45.8
Febrile neutropenia 13.8 7.6
Leukopenia 12.3 14.6
Diarrhea 7.9 5.0
Peripheral neuropathy 2.7 1.8
Left ventricular systolic dysfunction 1.2 2.8
Baselga J, et al. N Engl J Med. 2012;366:109-119.
Trastuzumab and Docetaxel ± Pertuzumab in HER2+
MBC (CLEOPATRA): Safety
47. CLEOPATRA: Survival With Pertuzumab,
Trastuzumab, and Docetaxel in HER2+ MBC
Swain. Lancet Oncol. 2020;21:519.
Landmark OS: 37%
Events: 235 (58.5%)
Landmark OS: 23%
Events: 280 (69.0%)
HR: 0.69 (95% CI: 0.58-0.82)
P = .0001
100
80
60
40
20
0
0 10 20 30 40 50 60 70 80 90 100 110 120 130
OS
(%)
Mo
P + H + D
PBO + H + D
402
406
371
350
318
289
269
230
228
181
188
149
165
115
150
96
137
88
120
75
71
44
20
11
0
1
0
0
57.1
40.8
Median OS,
Mo
P + H + D
PBO + H + D
End-of-Study OS in ITT Population*
8 yr
Patients at Risk, n
18.7
12.4
Median PFS,
Mo
P + H + D
PBO + H + D
Landmark PFS: 16%
Events: 304 (76%)
Landmark PFS: 10%; Events: 329 (81%)
HR: 0.69 (95% CI: 0.59-0.81)
P = .0001
100
80
60
40
20
0
0 10 20 30 40 50 60 70 80 90 100 110 120
PFS
(%)
Mo
402
406
284
223
179
110
121
76
93
53
71
43
60
35
52
30
43
23
34
21
21
10
6
4
0
0
End-of-Study PFS in ITT Population*
8 yr
*Crossover patients were analyzed in the placebo arm.
48. Centrally confirmed HER2-
positive locally recurrent,
unresectable or metastatic
BC (mBC)
≤1 hormonal regimen
for mBC
Prior (neo)adjuvant
systemic Rx including
trastuzumab allowed if
followed by DFS ≥12 mo
Baseline LVEF ≥50%;
no CHF or LVEF <50% during
or after prior trastuzumab
Trastuzumab (T)
Docetaxel (D) (≥6 cycles recommended)
Trastuzumab
Docetaxel (≥6 cycles recommended)
Placebo (Pla)
Pertuzumab (Ptz)
1:1
N = 406
N = 402
R
Primary endpoint: Independently assessed progression-free survival (PFS)
CLEOPATRA Study Design
Baselga J et al. N Engl J Med 2012;366(2):109-19.
49. Independently
assessed
Ptz + T + D
(n = 402)
Pla + T + D
(n = 406)
Hazard
ratio
p-
value
Median PFS 18.5 mo 12.4 mo 0.62 <0.001
Deaths in interim
overall survival
analysis, n (%)*
69 (17.2%) 96 (23.6%) 0.64 0.005
* Not significant because analysis did not meet O’Brien-Fleming stopping
boundary; a strong trend was evident toward overall survival benefit with
pertuzumab
CLEOPATRA: Primary
Efficacy Analysis
Baselga J et al. N Engl J Med 2012;366(2):109-19.
50. CLEOPATRA: Overall Survival (Confirmatory
Analysis)
• Crossed O’Brien-Fleming stopping boundary and was therefore deemed statistically
significant.
• Analysis was performed after 267 deaths and 69% of the prespecified total number
of events for the final analysis had occurred.
• Median follow-up in both arms = 30 months
With permission from Swain SM et al. Proc SABCS 2012;Abstract P5-18-26.
51. CLEOPATRA: Overall Survival in Predefined
Subgroups
With permission from Swain SM et al. Proc SABCS 2012;Abstract P5-18-26.
52. CLEOPATRA: Follow-Up Analysis — Updated
Investigator-Assessed PFS
• At the time of the data cutoff, 296 (72.9%) patients on the placebo arm and 257
(63.9%) on the pertuzumab arm had experienced a PFS event. These results
were exploratory only.
• This updated analysis of investigator-assessed PFS was consistent with the
results from the primary PFS analyses.
With permission from Swain SM et al. Proc SABCS 2012;Abstract P5-18-26.
53. CLEOPATRA: Select All-Grade
Adverse Events (AEs)
AEs with ≥25% incidence or
≥5% difference between arms
Ptz + T + D
(n = 408)
Pla + T + D
(n = 396)
Diarrhea 68.1% 48.2%
Rash 36.5% 24.0%
Mucosal inflammation 27.5% 19.9%
Peripheral edema 24.8% 30.8%
Pruritus 16.7% 10.1%
Constipation 15.4% 25.5%
Febrile neutropenia 13.7% 7.6%
Dry skin 10.8% 5.8%
Swain SM et al. Proc SABCS 2012;Abstract P5-18-26.
Ptz + T + D did not increase the incidence of cardiac adverse events compared to
Pla + T + D.
54. CLEOPATRA: Grade ≥3 Adverse Events
Grade ≥3 adverse events
(incidence ≥5%)
Ptz + T + D
(n = 408)
Pla + T + D
(n = 396)
Neutropenia 49.0% 46.0%
Febrile neutropenia 13.7% 7.6%
Leukopenia 12.3% 14.9%
Diarrhea 9.1% 5.1%
Swain SM et al. Proc SABCS 2012;Abstract P5-18-26.
Mucosal inflammation (Grade ≥3) was reported in 1% of patients in the placebo
arm and 1.5% of patients in the pertuzumab arm.
55. Author Conclusions
At the second interim analysis, CLEOPATRA demonstrated a
statistically significant and clinically meaningful improvement in
OS with the addition of pertuzumab to trastuzumab/docetaxel as
first-line therapy for HER2-positive mBC.
– As a consequence of the statistically significant survival benefit,
patients who were still receiving study treatment on the placebo
arm were offered crossover to the pertuzumab arm.
– The final exploratory analysis of OS is event driven and will take
place when 385 events have been reached.
No new safety signals compared to the primary analysis were
reported with 1 more year of follow-up.
These results indicate that combined HER2 blockade and
chemotherapy with pertuzumab/trastuzumab/docetaxel can be
considered a standard first-line therapy for patients with HER2-
positive mBC.
Swain SM et al. Proc SABCS 2012;Abstract P5-18-26.
56. Investigator Commentary: Confirmatory OS Analysis of
CLEOPATRA — Pertuzumab with Trastuzumab and Docetaxel as
First-Line Therapy for HER2-Positive mBC
Changes in the first-line setting for patients with mBC have been coming
along rapidly. The primary analysis of CLEOPATRA reported a significant
improvement in PFS, and, as expected, this current analysis reported an
improvement in OS. The authors confirmed little increase in toxicity
compared to dual taxane/trastuzumab therapy. This report solidifies that
the appropriate strategy is to administer a taxane in combination with
trastuzumab and pertuzumab in the first-line setting.
Recent data have shown similar efficacy with docetaxel/trastuzumab and
vinorelbine/trastuzumab but lower toxicity with the vinorelbine versus
the docetaxel combination. The results of CLEOPATRA have given us
impetus for an ongoing trial called VELVET that I have the honor of
leading. This Phase II trial is for patients who are eligible to receive first-
line therapy for HER2-positive mBC. In the first cohort, which we have
already enrolled, patients will receive pertuzumab and trastuzumab
sequentially. The second cohort will receive pertuzumab and
trastuzumab together. Vinorelbine will be given to both cohorts.
Interview with Edith A Perez, MD, January 17, 2013