The DESTINY-Breast04 trial is a Phase III randomized trial evaluating Enhertu compared to chemotherapy for previously treated HER2-low metastatic breast cancer. The trial randomized over 550 patients 2:1 to receive either Enhertu or one of several standard chemotherapy options. The primary endpoint is progression-free survival in the hormone receptor positive subgroup. Key secondary endpoints include overall survival in both the hormone receptor positive and total patient populations. Baseline characteristics were well balanced between the two arms. Results from this trial could establish Enhertu as a new treatment option for HER2-low breast cancer.
Elacestrant, an oral selective estrogen receptor degrader (SERD), showed improved progression-free survival compared to standard of care endocrine therapies in patients with ER-positive/HER2-negative metastatic breast cancer in the phase 3 EMERALD trial. In all patients and those with ESR1 mutations, elacestrant reduced the risk of progression or death by 30% and 45% respectively. Elacestrant was well tolerated with a safety profile consistent with other endocrine therapies and no treatment-related deaths. The results support elacestrant as a new oral treatment option for patients with advanced ER-positive breast cancer.
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.
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 document discusses selective estrogen receptor degraders (SERDs) for the treatment of HR+/HER2- breast cancer. It provides background on HR+/HER2- breast cancer and how SERDs work as a novel class of anti-estrogen drugs that degrade the estrogen receptor. Several key SERDs in clinical development are discussed, including elacestrant by Radius Pharmaceuticals and AZD9833 by AstraZeneca. Clinical strategies being evaluated for SERDs include combinations with CDK4/6 inhibitors and mTOR inhibitors. Many ongoing clinical trials are in phases 2 and 3, focusing on SERDs for the first and second line of therapy against breast cancer.
Management of hormonal resistant breast cancer Ahmed Allam
The document discusses endocrine therapy for breast cancer and mechanisms of resistance. It notes that around 60% of ER-positive breast cancer patients benefit from endocrine therapy like tamoxifen. Later studies found aromatase inhibitors and mTOR inhibitors can help overcome resistance. One study showed everolimus plus tamoxifen extended time to progression compared to tamoxifen alone in metastatic breast cancer patients previously treated with aromatase inhibitors.
1) The document discusses PARP inhibition in breast cancer, from preclinical rationale to clinical trials. It summarizes key trials like OlympiAD and EMBRACA which showed improved progression-free survival with PARP inhibitors olaparib and talazoparib in advanced BRCA-mutated breast cancer.
2) It also discusses the OlympiA trial, which is evaluating olaparib as adjuvant therapy in early-stage high-risk BRCA-mutated breast cancer patients to reduce the risk of disease recurrence.
3) Finally, it briefly touches on the increased rates of BRCA testing post the "Angelina Jolie effect" and the need to expand BRCA testing
ADC’s - What Everyone with MBC Should Know about Antibody Drug Conjugatesbkling
Antibody drug conjugates (ADC’s), a novel class of anticancer agents, have been around for decades but recently great strides have been made in metastatic breast cancer. Next generation ADC’s, sometimes referred to as ' Trojan Horses' have shown promising efficacy in all subtypes of MBC. Join Dr. Erika Hamilton, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, and partner with Tennessee Oncology PLCC, as she presents an overview of ADC’s, biomarkers and clinical mapping, current treatment options, as well as the promising trials to keep an eye on. There will be time for your questions throughout the presentation.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
Elacestrant, an oral selective estrogen receptor degrader (SERD), showed improved progression-free survival compared to standard of care endocrine therapies in patients with ER-positive/HER2-negative metastatic breast cancer in the phase 3 EMERALD trial. In all patients and those with ESR1 mutations, elacestrant reduced the risk of progression or death by 30% and 45% respectively. Elacestrant was well tolerated with a safety profile consistent with other endocrine therapies and no treatment-related deaths. The results support elacestrant as a new oral treatment option for patients with advanced ER-positive breast cancer.
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.
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 document discusses selective estrogen receptor degraders (SERDs) for the treatment of HR+/HER2- breast cancer. It provides background on HR+/HER2- breast cancer and how SERDs work as a novel class of anti-estrogen drugs that degrade the estrogen receptor. Several key SERDs in clinical development are discussed, including elacestrant by Radius Pharmaceuticals and AZD9833 by AstraZeneca. Clinical strategies being evaluated for SERDs include combinations with CDK4/6 inhibitors and mTOR inhibitors. Many ongoing clinical trials are in phases 2 and 3, focusing on SERDs for the first and second line of therapy against breast cancer.
Management of hormonal resistant breast cancer Ahmed Allam
The document discusses endocrine therapy for breast cancer and mechanisms of resistance. It notes that around 60% of ER-positive breast cancer patients benefit from endocrine therapy like tamoxifen. Later studies found aromatase inhibitors and mTOR inhibitors can help overcome resistance. One study showed everolimus plus tamoxifen extended time to progression compared to tamoxifen alone in metastatic breast cancer patients previously treated with aromatase inhibitors.
1) The document discusses PARP inhibition in breast cancer, from preclinical rationale to clinical trials. It summarizes key trials like OlympiAD and EMBRACA which showed improved progression-free survival with PARP inhibitors olaparib and talazoparib in advanced BRCA-mutated breast cancer.
2) It also discusses the OlympiA trial, which is evaluating olaparib as adjuvant therapy in early-stage high-risk BRCA-mutated breast cancer patients to reduce the risk of disease recurrence.
3) Finally, it briefly touches on the increased rates of BRCA testing post the "Angelina Jolie effect" and the need to expand BRCA testing
ADC’s - What Everyone with MBC Should Know about Antibody Drug Conjugatesbkling
Antibody drug conjugates (ADC’s), a novel class of anticancer agents, have been around for decades but recently great strides have been made in metastatic breast cancer. Next generation ADC’s, sometimes referred to as ' Trojan Horses' have shown promising efficacy in all subtypes of MBC. Join Dr. Erika Hamilton, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, and partner with Tennessee Oncology PLCC, as she presents an overview of ADC’s, biomarkers and clinical mapping, current treatment options, as well as the promising trials to keep an eye on. There will be time for your questions throughout the presentation.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
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
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
Dr. Jennifer Mueller, gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, will share research updates on uterine/endometrial cancer and other new developments in treatment and surgery.
Immunotherapy for Metastatic Triple Negative Breast Cancerbkling
Sylvia Adams, MD, medical oncologist, and associate professor at the NYU School of Medicine, discusses the latest research including the role of immunology in the treatment of triple negative metastatic breast cancer. This webinar was hosted on October 19, 2016.
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
This document discusses targeted cancer therapy and provides several examples. It compares chemotherapy to targeted therapy, noting targeted therapy drugs inhibit more specific targets and include many oral agents. Examples discussed include Gleevec for CML targeting BCR-ABL fusion, EGFR mutations in lung cancer treated by drugs like Iressa, ALK rearrangements in lung cancer treated by crizotinib, BRAF mutations in melanoma treated by vemurafenib, and HER2-positive breast cancers treated by Herceptin. New immunotherapies and antibody-drug conjugates are also mentioned.
The document summarizes several targeted therapies for breast cancer including monoclonal antibodies (trastuzumab, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, pertuzumab, margetuximab-cmkb), antibody-drug conjugates (ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, sacituzumab govitecan), immune checkpoint inhibitors (pembrolizumab, atezolizumab), and PARP inhibitors (olaparib). It provides details on the mechanisms of action, FDA-approved indications, dosing schedules, and safety profiles of these targeted therapies.
- The document discusses breast-conserving therapy (BCT) for breast cancer as an alternative to mastectomy, summarizing the results of several randomized trials finding no difference in disease-free or overall survival between the two approaches.
- Positive margins after lumpectomy, extensive intraductal component, and tumor stage determine appropriate use of radiotherapy after BCT or mastectomy. Dose and technique for radiotherapy are described for different breast cancer stages and situations.
- Post-mastectomy radiotherapy reduces local recurrence risk and provides a survival benefit according to meta-analyses, with indications outlined for different patient subgroups. Complications of radiotherapy are discussed as well as ongoing trials of partial breast irradiation techniques.
This document discusses the management of early HER2+ breast cancer. It defines early breast cancer and describes the HER2+ subtype, which accounts for around 25% of cases. For early HER2+ breast cancer, neoadjuvant chemotherapy plus trastuzumab improves pathological complete response rates and long-term outcomes compared to chemotherapy alone. Multiple trials demonstrate the benefit of adding pertuzumab or T-DM1 to neoadjuvant regimens. Post-neoadjuvant surgery may require close evaluation of margins due to heterogeneous response.
This document discusses targeted cancer therapies and their mechanisms of action. It outlines 10 hallmarks of cancer and describes targeted drugs that inhibit specific proteins and pathways involved in cancer growth. These targeted drugs include small molecule tyrosine kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, and proteosome inhibitors. Examples are provided of targeted therapies used to treat cancers like chronic myeloid leukemia, lung cancer, breast cancer, and multiple myeloma. Potential side effects of targeted therapies are also mentioned.
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
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
Her2Neu positive breast cancer is comprises of about 15-20% of all breast cancer. Among them quite a few number of patients present as de novo metastasis . In this presentation you ll find a guide how to manage it with relevant evidences. Presentation is meant for Oncology trainees.
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.
Hitting the Target in HER2-Positive Metastatic Colorectal Canceri3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck will share the latest data and strategies for hitting the target in HER2-positive metastatic colorectal cancer. Dr. Christopher Lieu, Associate Professor at the University of Colorado Cancer Center, explores actionable targets to inform personalized care plans, guideline-recommended combination and sequencing strategies, adverse event monitoring and management, and more.
STATEMENT OF NEED
An estimated 153,020 new cases of colorectal cancer (CRC) are diagnosed annually, and 52,550 people die of the disease (Siegel et al, 2023). Approximately 22% of patients present with metastatic disease, which is associated with a dismal 5-year survival rate of 15% (SEER, 2022). Targeting biomarkers is a key strategy for expanding therapeutic options and improving outcomes in metastatic CRC. Human epidermal growth factor receptor 2 (HER2) amplification status and treatments targeting HER2 are some of the most recent additions to the arsenal of targeted therapy for this disease. This activity chaired by Christopher Lieu, MD, Associate Director of Clinical Research at the University of Colorado Cancer Center, will provide expert perspectives and practical guidance on treating HER2-positive metastatic CRC.
TARGET AUDIENCE
Oncologists, gastroenterologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with colorectal cancer (CRC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish actionable targets that can inform personalized care plans in metastatic CRC
Evaluate practice guidelines on treatment combinations and sequences for patients with metastatic CRC
Appraise emerging efficacy and safety data on novel targeted therapies for patients with HER2-positive metastatic CRC
Assess strategies for optimizing the safety and tolerability of novel targeted therapies for HER2-positive metastatic CRC
The OUTBACK trial compared standard chemoradiation (CRT) to CRT plus adjuvant carboplatin and paclitaxel (ACT) in patients with locally advanced cervical cancer. Over 900 patients were randomized 1:1 to receive either CRT alone or CRT followed by ACT. Baseline characteristics were well balanced between the two arms. The primary endpoint was overall survival and secondary endpoints included progression-free survival, adverse events, sites of recurrence, and patient-reported outcomes.
This document discusses targeted cancer therapy. It begins with an introduction to cancer classification and targeted therapy. It then discusses the epidemiology of cancer in India, signs and symptoms, and risk factors. It describes the goals and challenges of targeted therapy development. Targets for targeted therapy include monoclonal antibodies and small molecule inhibitors that target proteins involved in cancer signaling pathways. Treatment involves administration of targeted drugs through pills or IV. Side effects and limitations of targeted therapy are also discussed. The document concludes that targeted therapies provide more selective treatment compared to chemotherapy.
This document discusses targeted therapy for breast cancer. It begins by providing background on declining mortality rates for breast cancer over time. It then discusses how cancers develop multiple alterations that allow uncontrolled growth and outlines six essential alterations in cell physiology that contribute to malignancy. The document discusses molecular alterations that occur in breast cancer progression. It defines targeted therapy as drugs that target uniquely disrupted pathways in cancer cells. The document outlines several targeted therapies for breast cancer including hormonal therapies like tamoxifen, aromatase inhibitors, and fulvestrant. It discusses clinical trials demonstrating the benefits of these therapies. It also discusses therapies that target the HER2 receptor like trastuzumab and lapatinib. In summary, the document provides an overview of targeted
The CLEOPATRA trial was a phase III randomized controlled trial that compared the efficacy and safety of pertuzumab, trastuzumab, and docetaxel versus placebo, trastuzumab, and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer. The study found that adding pertuzumab to trastuzumab and docetaxel significantly extended progression-free survival by 6 months and improved overall response rates compared to the placebo group. Overall survival was also improved with the pertuzumab regimen. While rates of adverse events were similar between the groups, the pertuzumab regimen represented a substantial improvement over the standard of care.
This document summarizes various targeted anticancer therapies. It discusses targeted therapies that interfere with molecular structures implicated in tumor growth like nuclear factors, cell survival factors, and angiogenesis factors. Primary targeted therapy tools are monoclonal antibodies and small synthetic molecules. Protein kinases and their role in signaling pathways are described. Examples of targeted therapies discussed include BCR-ABL tyrosine kinase inhibitors, EGFR inhibitors, HER2/NEU inhibitors, angiogenesis inhibitors targeting VEGF, mTOR inhibitors, proteasome inhibitors, MAPK pathway inhibitors, and monoclonal antibodies. Resistance mechanisms and newer agents to overcome resistance are also summarized.
- IDXG provides molecular diagnostic tests for cancer risk assessment and prognosis.
- Recent accomplishments include new product launches, reimbursement from Aetna for ThyraMir, and achieving approval in New York State.
- The presentation provides financial information, with revenue growing but losses continuing from investments in sales, R&D and administrative expenses.
Merck presented at the 2016 ASCO conference on their oncology strategy and KEYTRUDA program. Key points include:
1) Merck's strategy is to identify patients most likely to benefit from KEYTRUDA, establish KEYTRUDA as a foundation for cancer treatment in monotherapy and combinations, and improve long-term disease control and survival across cancers.
2) KEYTRUDA has shown clinical activity in over 20 tumor types and has over 30 ongoing registration-enabling studies and 100 combination trials. Data at ASCO 2016 showed further progress in combinations and predictive biomarkers.
3) Merck is pursuing a combination strategy with KEYTRUDA and targeted therapies, immunomodulators
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
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
Dr. Jennifer Mueller, gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, will share research updates on uterine/endometrial cancer and other new developments in treatment and surgery.
Immunotherapy for Metastatic Triple Negative Breast Cancerbkling
Sylvia Adams, MD, medical oncologist, and associate professor at the NYU School of Medicine, discusses the latest research including the role of immunology in the treatment of triple negative metastatic breast cancer. This webinar was hosted on October 19, 2016.
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
This document discusses targeted cancer therapy and provides several examples. It compares chemotherapy to targeted therapy, noting targeted therapy drugs inhibit more specific targets and include many oral agents. Examples discussed include Gleevec for CML targeting BCR-ABL fusion, EGFR mutations in lung cancer treated by drugs like Iressa, ALK rearrangements in lung cancer treated by crizotinib, BRAF mutations in melanoma treated by vemurafenib, and HER2-positive breast cancers treated by Herceptin. New immunotherapies and antibody-drug conjugates are also mentioned.
The document summarizes several targeted therapies for breast cancer including monoclonal antibodies (trastuzumab, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, pertuzumab, margetuximab-cmkb), antibody-drug conjugates (ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, sacituzumab govitecan), immune checkpoint inhibitors (pembrolizumab, atezolizumab), and PARP inhibitors (olaparib). It provides details on the mechanisms of action, FDA-approved indications, dosing schedules, and safety profiles of these targeted therapies.
- The document discusses breast-conserving therapy (BCT) for breast cancer as an alternative to mastectomy, summarizing the results of several randomized trials finding no difference in disease-free or overall survival between the two approaches.
- Positive margins after lumpectomy, extensive intraductal component, and tumor stage determine appropriate use of radiotherapy after BCT or mastectomy. Dose and technique for radiotherapy are described for different breast cancer stages and situations.
- Post-mastectomy radiotherapy reduces local recurrence risk and provides a survival benefit according to meta-analyses, with indications outlined for different patient subgroups. Complications of radiotherapy are discussed as well as ongoing trials of partial breast irradiation techniques.
This document discusses the management of early HER2+ breast cancer. It defines early breast cancer and describes the HER2+ subtype, which accounts for around 25% of cases. For early HER2+ breast cancer, neoadjuvant chemotherapy plus trastuzumab improves pathological complete response rates and long-term outcomes compared to chemotherapy alone. Multiple trials demonstrate the benefit of adding pertuzumab or T-DM1 to neoadjuvant regimens. Post-neoadjuvant surgery may require close evaluation of margins due to heterogeneous response.
This document discusses targeted cancer therapies and their mechanisms of action. It outlines 10 hallmarks of cancer and describes targeted drugs that inhibit specific proteins and pathways involved in cancer growth. These targeted drugs include small molecule tyrosine kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, and proteosome inhibitors. Examples are provided of targeted therapies used to treat cancers like chronic myeloid leukemia, lung cancer, breast cancer, and multiple myeloma. Potential side effects of targeted therapies are also mentioned.
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
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
Her2Neu positive breast cancer is comprises of about 15-20% of all breast cancer. Among them quite a few number of patients present as de novo metastasis . In this presentation you ll find a guide how to manage it with relevant evidences. Presentation is meant for Oncology trainees.
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.
Hitting the Target in HER2-Positive Metastatic Colorectal Canceri3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck will share the latest data and strategies for hitting the target in HER2-positive metastatic colorectal cancer. Dr. Christopher Lieu, Associate Professor at the University of Colorado Cancer Center, explores actionable targets to inform personalized care plans, guideline-recommended combination and sequencing strategies, adverse event monitoring and management, and more.
STATEMENT OF NEED
An estimated 153,020 new cases of colorectal cancer (CRC) are diagnosed annually, and 52,550 people die of the disease (Siegel et al, 2023). Approximately 22% of patients present with metastatic disease, which is associated with a dismal 5-year survival rate of 15% (SEER, 2022). Targeting biomarkers is a key strategy for expanding therapeutic options and improving outcomes in metastatic CRC. Human epidermal growth factor receptor 2 (HER2) amplification status and treatments targeting HER2 are some of the most recent additions to the arsenal of targeted therapy for this disease. This activity chaired by Christopher Lieu, MD, Associate Director of Clinical Research at the University of Colorado Cancer Center, will provide expert perspectives and practical guidance on treating HER2-positive metastatic CRC.
TARGET AUDIENCE
Oncologists, gastroenterologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with colorectal cancer (CRC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish actionable targets that can inform personalized care plans in metastatic CRC
Evaluate practice guidelines on treatment combinations and sequences for patients with metastatic CRC
Appraise emerging efficacy and safety data on novel targeted therapies for patients with HER2-positive metastatic CRC
Assess strategies for optimizing the safety and tolerability of novel targeted therapies for HER2-positive metastatic CRC
The OUTBACK trial compared standard chemoradiation (CRT) to CRT plus adjuvant carboplatin and paclitaxel (ACT) in patients with locally advanced cervical cancer. Over 900 patients were randomized 1:1 to receive either CRT alone or CRT followed by ACT. Baseline characteristics were well balanced between the two arms. The primary endpoint was overall survival and secondary endpoints included progression-free survival, adverse events, sites of recurrence, and patient-reported outcomes.
This document discusses targeted cancer therapy. It begins with an introduction to cancer classification and targeted therapy. It then discusses the epidemiology of cancer in India, signs and symptoms, and risk factors. It describes the goals and challenges of targeted therapy development. Targets for targeted therapy include monoclonal antibodies and small molecule inhibitors that target proteins involved in cancer signaling pathways. Treatment involves administration of targeted drugs through pills or IV. Side effects and limitations of targeted therapy are also discussed. The document concludes that targeted therapies provide more selective treatment compared to chemotherapy.
This document discusses targeted therapy for breast cancer. It begins by providing background on declining mortality rates for breast cancer over time. It then discusses how cancers develop multiple alterations that allow uncontrolled growth and outlines six essential alterations in cell physiology that contribute to malignancy. The document discusses molecular alterations that occur in breast cancer progression. It defines targeted therapy as drugs that target uniquely disrupted pathways in cancer cells. The document outlines several targeted therapies for breast cancer including hormonal therapies like tamoxifen, aromatase inhibitors, and fulvestrant. It discusses clinical trials demonstrating the benefits of these therapies. It also discusses therapies that target the HER2 receptor like trastuzumab and lapatinib. In summary, the document provides an overview of targeted
The CLEOPATRA trial was a phase III randomized controlled trial that compared the efficacy and safety of pertuzumab, trastuzumab, and docetaxel versus placebo, trastuzumab, and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer. The study found that adding pertuzumab to trastuzumab and docetaxel significantly extended progression-free survival by 6 months and improved overall response rates compared to the placebo group. Overall survival was also improved with the pertuzumab regimen. While rates of adverse events were similar between the groups, the pertuzumab regimen represented a substantial improvement over the standard of care.
This document summarizes various targeted anticancer therapies. It discusses targeted therapies that interfere with molecular structures implicated in tumor growth like nuclear factors, cell survival factors, and angiogenesis factors. Primary targeted therapy tools are monoclonal antibodies and small synthetic molecules. Protein kinases and their role in signaling pathways are described. Examples of targeted therapies discussed include BCR-ABL tyrosine kinase inhibitors, EGFR inhibitors, HER2/NEU inhibitors, angiogenesis inhibitors targeting VEGF, mTOR inhibitors, proteasome inhibitors, MAPK pathway inhibitors, and monoclonal antibodies. Resistance mechanisms and newer agents to overcome resistance are also summarized.
- IDXG provides molecular diagnostic tests for cancer risk assessment and prognosis.
- Recent accomplishments include new product launches, reimbursement from Aetna for ThyraMir, and achieving approval in New York State.
- The presentation provides financial information, with revenue growing but losses continuing from investments in sales, R&D and administrative expenses.
Merck presented at the 2016 ASCO conference on their oncology strategy and KEYTRUDA program. Key points include:
1) Merck's strategy is to identify patients most likely to benefit from KEYTRUDA, establish KEYTRUDA as a foundation for cancer treatment in monotherapy and combinations, and improve long-term disease control and survival across cancers.
2) KEYTRUDA has shown clinical activity in over 20 tumor types and has over 30 ongoing registration-enabling studies and 100 combination trials. Data at ASCO 2016 showed further progress in combinations and predictive biomarkers.
3) Merck is pursuing a combination strategy with KEYTRUDA and targeted therapies, immunomodulators
Prescient Therapeutics (PTX:ASX) is an ASX-listed biotechnology company focused on improving outcomes for cancer patients by developing personal medicines, using CAR-T and targeted therapy approaches.
Universal CAR-T therapies like OmniCAR have the potential to take personalised cancer treatment to the next level, by combining the cancer-killing capabilities of a T-cell with the control and pharmacology of a drug.
This presentation provides an overview of Interpace Diagnostics Group (IDXG), a commercial company that provides molecular diagnostic tests and pathology services. Key points:
- IDXG has proprietary molecular diagnostic tests for pancreatic cysts (PancraGEN), thyroid nodules (ThyGenX/ThyraMIR), and Barrett's esophagus (BarreGEN).
- Clinical studies show PancraGEN more accurately determines cancer risk of pancreatic cysts compared to current guidelines. ThyGenX/ThyraMIR combination testing can accurately rule in or rule out thyroid cancer risk.
- The tests have significant market opportunities and address unmet clinical needs to avoid unnecessary surgeries and
This document provides an overview of Cancer Genetics, Inc. It discusses the company's focus on empowering personalized cancer treatment through molecular diagnostics. The summary highlights Cancer Genetics' proprietary diagnostic products for various cancers, partnerships with biopharma companies, growth in revenue and testing volume in 2013, and pipeline of diagnostic tests in development. It also outlines the company's business model and strategy to commercialize its products to target markets globally.
An oncology-focused immunotherapy company is conducting a Phase 3 clinical trial of its lead product, NeuVax, for the prevention of breast cancer recurrence in early-stage, node-positive patients. The trial is fully enrolled with 758 participants and is evaluating NeuVax compared to placebo on disease-free survival. NeuVax targets the HER2 protein and consists of an HLA-A2/A3-restricted peptide that elicits CD8+ T-cell responses. Previous clinical trials demonstrated NeuVax has a positive safety profile and signals of efficacy in reducing recurrence rates. An interim analysis is upcoming in mid-2016, with final results expected in 2018.
This presentation provides an overview of Interpace Diagnostics Group (IDXG), a commercial company that provides molecular diagnostic tests and pathology services for cancer evaluation. IDXG operates two CLIA-certified labs and has four proprietary molecular diagnostic tests for pancreatic cysts and thyroid nodules that assess cancer risk. The tests have high margins and barriers to entry due to reimbursement and complexity. Recent accomplishments include raising funds, improving financials, expanding insurance coverage and launching international distribution. The molecular diagnostic market is large and growing due to advantages over drug development. IDXG's tests establish new standards in cancer risk assessment for pancreatic cysts and thyroid nodules compared to current guidelines.
This presentation provides an overview of an oncology-focused immunotherapy company. It discusses the company's lead product, NeuVax, which is an immunotherapy targeting HER2-positive breast cancer currently in a Phase 3 clinical trial. The presentation summarizes the clinical development pipeline, mechanism of action involving T-cell activation, positive safety profile established in previous trials, and potential commercial opportunities. It also briefly discusses the company's pipeline of products targeting other cancers, including GALE-301 and GALE-302 which target Folate Binding Protein in ovarian and endometrial cancers.
This presentation provides an overview of an oncology-focused immunotherapy company. It discusses the company's lead product, NeuVax, which is an immunotherapy targeting HER2-positive breast cancer in both the adjuvant and metastatic settings. Key information includes:
- NeuVax is currently in a Phase 3 clinical trial (PRESENT) in the adjuvant setting for HER2 1+/2+ breast cancer patients. Enrollment is complete for the trial.
- An interim analysis of the PRESENT trial is expected in late Q2 2016 which will evaluate safety and futility based on 70 recurrence events.
- Additional clinical trials are exploring NeuVax in combination with Herceptin and in other HER2-positive cancers like
This presentation provides an overview of an oncology-focused immunotherapy company. It discusses the company's lead product, NeuVax, which is an immunotherapy targeting HER2-positive breast cancer in both the adjuvant and metastatic settings. Key information includes:
- NeuVax is currently in a Phase 3 clinical trial (PRESENT) in the adjuvant setting for HER2 1+/2+ breast cancer patients. Enrollment is complete for the trial.
- An interim analysis of the PRESENT trial is expected in late Q2 2016 which will evaluate safety and futility based on 70 recurrence events.
- Additional clinical trials are exploring NeuVax in combination with Herceptin and in other HER2-positive cancers like
This presentation provides an overview of an oncology-focused immunotherapy company. It discusses the company's lead product, NeuVax, which is an immunotherapy targeting HER2-positive breast cancer in both the adjuvant and metastatic settings. Key information includes:
- NeuVax is currently in a Phase 3 clinical trial (PRESENT) in the adjuvant setting for HER2 1+/2+ breast cancer to prevent disease recurrence.
- Additional trials are planned or ongoing to study NeuVax in combination with Herceptin and in other HER2-positive cancers like gastric cancer.
- NeuVax works by stimulating cytotoxic T-cells to seek out and destroy tumor cells expressing HER2 and has shown a good safety profile
This corporate presentation outlines Aura Biosciences' novel targeted therapy approach using viral-like particles to treat cancer. Their lead product, AU-011, is being developed for the treatment of ocular melanoma, an orphan disease with no approved therapies. Preclinical data shows AU-011 effectively targets and kills tumor cells through a unique mechanism of action. Aura plans to initiate clinical trials in Q1-2/2016 to obtain proof of concept data and accelerate approval. If approved, AU-011 could be the first FDA-approved treatment for the primary tumor in ocular melanoma patients.
Exact Sciences Corporate Presentation: June 2016Exact Sciences
- The corporate presentation provides an overview of the company's mission to help eradicate colon cancer through partnerships with various stakeholders. It highlights key facts about colon cancer incidence and mortality rates.
- Cologuard, the company's non-invasive stool DNA screening test, is described as addressing the colon cancer challenge through multi-target screening with high sensitivity and specificity rates confirmed in clinical studies.
- The presentation outlines the large market opportunity for Cologuard given the underutilized colon cancer screening rates in the US and Cologuard's inclusion in medical guidelines and recommendations.
Exact Sciences Company Presentation Baird Healthcare ConferenceExact Sciences
Exact Sciences CEO Kevin Conroy's presentation slides, featuring updates on Cologuard's commercial launch, from the 2014 Baird Healthcare Conference September 4, 2014.
Slide deck used by Dr. Wayne Danter, President and CEO of Critical Outcome Technologies, at the Equities.com Small-Cap Stars investor conference in New York City on June 10, 2015.
Genetic Technologies Limited (ASX: GTG; Nasdaq: GENE), a diversified molecular diagnostics company. GTG offers cancer predictive testing and assessment tools to help physicians proactively manage patient health. The Company’s lead products GeneType for Breast Cancer and GeneType for Colorectal Cancer are clinically validated risk assessment tests and are first in class. Genetic Technologies is developing a pipeline of risk assessment products. Learn more at GENETechinfo.com.
- PTX has a deep clinical pipeline with 3 ongoing or planned clinical trials, including Phase Ib/II trials of PTX-200 in breast cancer and ovarian cancer, and a planned Phase Ib trial of PTX-100 in AML.
- PTX-200 and PTX-100 are novel cancer drugs targeting the Akt and Ras pathways that have potential to overcome chemotherapy resistance.
- The clinical trials are being conducted at prestigious cancer centers in the US including Moffitt Cancer Center and Albert Einstein College of Medicine.
This corporate presentation summarizes PharmaMar's pipeline and strategy:
- PharmaMar is a biotech company focused on developing marine-derived oncology drugs. It has a fully integrated platform from discovery to commercialization.
- The pipeline includes Yondelis® for soft tissue sarcoma and ovarian cancer, Aplidin® for multiple myeloma, and PM1183 which is being studied in small cell lung cancer, platinum-resistant ovarian cancer, and BRCA breast cancer.
- PM1183 has shown promising results in early clinical trials, achieving a 67% response rate in small cell lung cancer. Phase III trials are ongoing in platinum-resistant ovarian cancer.
The document is an investor presentation by Antares Pharma discussing its business and growth strategy. It summarizes that Antares has a diversified revenue mix from proprietary, partner, and development products. It achieved $184 million in revenue in 2021 and guides to $200-220 million in 2022. It is focusing on urology and endocrinology areas with innovative products like XYOSTED and NOCDURNA. XYOSTED is an once weekly testosterone injection that has seen growing prescription trends. The presentation outlines Antares' strategy to expand partnerships and its proprietary product portfolio to drive continued financial growth.
The document provides an overview of the pharmaceutical R&D pipeline in 2022, including key trends and statistics. Some of the main points summarized are:
- The total drug development pipeline grew by 8.2% in 2022 to over 20,000 drugs, with most growth occurring in early stages. Cancer remains the dominant therapeutic area.
- 2021 saw a record number of new drug launches, with 97 new active substances approved. Cancer drugs accounted for many novel launches, along with treatments for COVID-19, autoimmune diseases, and other areas.
- The top 10 pharmaceutical companies by pipeline size saw little change, with Novartis, Roche, and Takeda maintaining the top spots. Cancer remains
Novartis announced a new organizational model to power its next phase of innovation, growth, and productivity. Key elements include:
1) Integrating Pharma and Oncology into a single Innovative Medicines business with separate US and International units to increase focus and drive synergies.
2) Combining strategy, portfolio management, and business development into a new Strategy & Growth function to strengthen the pipeline.
3) Forming a single Operations unit and integrating global G&A functions to realize economies of scale and productivity gains.
The changes aim to make Novartis more competitive, enhance operational efficiencies, and deliver high value medicines to support consistent above-peer growth.
Natco Pharma Limited is an integrated pharmaceutical company with operations across India, the US, and rest of world. It has a strong brand presence in oncology in India and is growing its portfolio in cardiology and diabetes. The company focuses on complex generics for the US market through niche Paragraph IV and Paragraph III filings. It has two R&D centers with over 525 employees and is poised for growth in the agricultural chemicals space. For the financial year ending March 2021, Natco Pharma reported total revenues of INR 21,557 million.
The document provides an investor presentation for Sun Pharmaceutical Industries Limited. It summarizes Sun Pharma's position as the 4th largest global specialty generic company, with a presence in over 100 countries. It outlines Sun Pharma's long-term strategy of enhancing its specialty business portfolio and achieving differentiation through complex products. The presentation provides details on Sun Pharma's revenue composition, history of growth and acquisitions, operations, and financial performance.
Roche and Genentech are leading healthcare companies dedicated to innovation in a sustainable way. Roche was founded in 1896 in Basel and still has majority family ownership. It has over 100,000 employees worldwide and sales of 62.8 billion CHF in 2021. Roche invests heavily in R&D and healthcare and was among the top companies in the Dow Jones Sustainability Index for 13 consecutive years. Genentech was the first publicly-owned biotech company. Roche has a unique innovation model with independent research centers worldwide and global product development, manufacturing, and commercialization. It manages over 250 partnerships and is optimally positioned as the leader in personalized healthcare through diagnostics, therapies, and decision support. Roche Partnering has
Mayne Pharma announced the proposed sale of its Metrics Contract Services business for US$475 million. The sale will allow Mayne Pharma to focus on building its dermatology and women's health product portfolios. Mayne Pharma intends to use the majority of the sale proceeds to repay debt and return excess funds to shareholders through initiatives like a capital return or special dividend. The sale is expected to strengthen Mayne Pharma's balance sheet and financial flexibility.
The document provides updates from Managed Health Services (MHS), an Indiana Medicaid health plan, including:
- COVID-19 policy changes have been rescinded and MHS will reimburse providers for COVID-19 vaccine counseling.
- MHS offers daily inpatient and discharge reports, and weekly medical and prescription claims reports to help providers monitor their patients.
- Provider incentives are offered for activities like pregnancy notifications and smoking cessation counseling.
- Changes to prior authorization requirements for outpatient behavioral health therapy now follow a calendar year limitation.
- MHS encourages coordination between behavioral and physical health providers and offers related training.
- New provider enrollment requests and additions to existing contracts will now be effective
This document is an investor presentation for AMN Healthcare that provides an overview of the company. Some key points:
- AMN Healthcare is a leader and innovator in total talent solutions for healthcare, providing staffing, workforce solutions, leadership and physician search, and talent management services.
- Over 60% of AMN's revenue comes from managed services programs (MSPs) where they provide comprehensive staffing and workforce solutions to health systems.
- AMN has transformed from primarily a diversified staffing company in 2008 to a strategic partner providing a full spectrum of innovative workforce solutions to major health systems in 2022.
- They aim to become the total talent solutions partner for clients by enhancing their digital
The document provides information from the 2022 DHA Industry Day, including:
- A list of requirements presented by different DHA directorates, such as medical logistics, enterprise medical services, administration and management, and information operations.
- The agenda for the industry day, including opening remarks, office briefings, and presentations from various DHA directorates.
- A discussion of the Defense Health Agency's transition and optimization efforts, including establishing markets, certifying market offices, realigning military treatment facilities, and pursuing ongoing market and DHA optimization.
- Healius reported record underlying results for 1H 2022 underpinned by Pathology's role in COVID testing and good cost control.
- The company is positioned for growth as routine healthcare demand rebounds from underdiagnosis during the pandemic. COVID testing volumes are also expected to remain at baseline levels.
- A strong interim dividend was declared and the company has a robust balance sheet to fund further growth opportunities like the Agilex Biolabs acquisition and Murdoch Day Hospital development.
Tenet Healthcare's CEO presented at the J.P. Morgan Healthcare Conference on January 11, 2022. Over the past several years, Tenet has transformed its portfolio, restructured operations, and improved quality and safety outcomes. It has demonstrated resiliency during the COVID-19 pandemic by consistently meeting or beating quarterly earnings guidance. Tenet aims to continue this growth trajectory by enhancing specialty care access, scaling its ambulatory surgery platform, and leading new high acuity services in lower cost settings.
Apollo Hospitals Enterprise Limited is a leading private healthcare services provider in India with over 6 decades of operations. It operates 71 hospitals with close to 10,000 beds across India and has expanded access to affordable healthcare through various initiatives. Apollo has played a pivotal role in developing the private healthcare sector in India by improving clinical outcomes and attracting medical talent both from India and overseas. Going forward, the company aims to continue its growth through a focus on clinical excellence, digital healthcare, and expansion into underserved markets.
Novo Nordisk presented highlights from the first six months of 2022. Their diabetes value market share increased 1.5 percentage points to 31%. Obesity care sales grew 84% driven by GLP-1 and insulin growth. They aim to further innovation in diabetes treatment, obesity, and rare diseases. Financial results were positive with 16% sales growth, 14% operating profit growth, and DKK 42.7 billion in free cash flow.
1) This training presentation provides guidance to research coordinators on clinical trial data collection and management best practices.
2) It reviews key definitions like source documents and case report forms, the lifecycle of developing a data management plan, and tips for proper documentation.
3) Ensuring data integrity involves accurate data entry from source documents to case report forms by coordinators, with oversight from principal investigators and monitoring by sponsors to meet regulatory standards.
This document outlines the key sections and content of a medical research paper, including reporting guidelines. It discusses sections like the title, abstract, introduction, methods, results, discussion, and conclusions. The methods section should describe the study design, participants, interventions, outcomes, and statistical analysis. The results section should report answers to the study questions using text, tables, and figures. The discussion should interpret the findings in the context of other research and discuss implications and recommendations. Reporting guidelines provide standards for transparently reporting different types of studies and their methodology.
1) The document provides tips for writing a high quality medical research paper, including how to structure the paper and what content to include in each section.
2) Key sections of a research paper are outlined, including the Introduction, Methods, Results, and Discussion sections. Guidance is given on what information should be included in each section.
3) Advice is given on writing clearly and concisely, using proper formatting, and focusing on quality over quantity. Following guidelines for target journals and ethical writing standards is emphasized.
Omega Healthcare Investors is a healthcare REIT that owns and leases skilled nursing and senior housing facilities. This presentation provides an overview of Omega's portfolio, strategy, and the skilled nursing facility industry. The key points are:
1) Omega has a large, geographically diversified portfolio of 939 healthcare properties across 43 U.S. states and the UK, leased to 63 different operators under long-term triple net leases.
2) Skilled nursing facilities provide essential healthcare services and meet an increasing demand from an aging population within a regulated industry with barriers to new supply growth.
3) Omega focuses on maintaining a conservative balance sheet, consistent dividend growth, and pursuing accretive investment opportunities to
The document is a Q2 FY18 investor presentation for HealthCare Global Enterprises Limited. Some key points:
- Q2 revenue grew 21.3% year-over-year to INR 2,111 million driven by growth in HCG and Milann centers.
- Q2 EBITDA increased 22.3% to INR 311 million with margins of 14.7%. Existing centers saw an EBITDA margin of 18.8%.
- New centers commissioned after April 2015 contributed revenues of INR 314 million but remained loss-making in Q2.
- GE is planning to spin off its healthcare business to become a standalone company called GE HealthCare in early January 2023.
- GE HealthCare is a global leader in medical technologies and digital solutions with over $18B in annual revenue and operations in over 160 countries.
- As an independent company, GE HealthCare aims to accelerate revenue growth, expand margins to a high-teens to 20% range through business optimization, and generate strong free cash flow to create sustainable long-term shareholder value.
R3 Stem Cell Therapy: A New Hope for Women with Ovarian FailureR3 Stem Cell
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This particular slides consist of- what is Pneumothorax,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is a summary of Pneumothorax:
Pneumothorax, also known as a collapsed lung, is a condition that occurs when air leaks into the space between the lung and chest wall. This air buildup puts pressure on the lung, preventing it from expanding fully when you breathe. A pneumothorax can cause a complete or partial collapse of the lung.
About this webinar: This talk will introduce what cancer rehabilitation is, where it fits into the cancer trajectory, and who can benefit from it. In addition, the current landscape of cancer rehabilitation in Canada will be discussed and the need for advocacy to increase access to this essential component of cancer care.
Comprehensive Rainy Season Advisory: Safety and Preparedness Tips.pdfDr Rachana Gujar
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Healthy Eating Habits:
Understanding Nutrition Labels: Teaches how to read and interpret food labels, focusing on serving sizes, calorie intake, and nutrients to limit or include.
Tips for Healthy Eating: Offers practical advice such as incorporating a variety of foods, practicing moderation, staying hydrated, and eating mindfully.
Benefits of Regular Exercise:
Physical Benefits: Discusses how exercise aids in weight management, muscle and bone health, cardiovascular health, and flexibility.
Mental Benefits: Explains the psychological advantages, including stress reduction, improved mood, and better sleep.
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Encourages consistency, variety in exercises, setting realistic goals, and finding enjoyable activities to maintain motivation.
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Integrating Nutrition and Exercise: Suggests meal planning and incorporating physical activity into daily routines.
Monitoring Progress: Recommends tracking food intake and exercise, regular health check-ups, and provides tips for achieving balance, such as getting sufficient sleep, managing stress, and staying socially active.
This particular slides consist of- what is hypotension,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is the summary of hypotension:
Hypotension, or low blood pressure, is when the pressure of blood circulating in the body is lower than normal or expected. It's only a problem if it negatively impacts the body and causes symptoms. Normal blood pressure is usually between 90/60 mmHg and 120/80 mmHg, but pressures below 90/60 are generally considered hypotensive.
2024 HIPAA Compliance Training Guide to the Compliance OfficersConference Panel
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ASCO-2022-IR-Presentation.pdf
1. Meet AZN management:
American Society of
Clinical Oncology
(ASCO) Cancers
Symposium 2022
For investors and analysts
6 June 2022
2. Forward-looking statements
In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act of 1995, AstraZeneca (hereafter ‘the Group’) provides the
following cautionary statement: this document contains certain forward-looking statements with respect to the operations, performance and financial condition of the Group,
including, among other things, statements about expected revenues, margins, earnings per share or other financial or other measures. Although the Group believes its expectations
are based on reasonable assumptions, any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual
outcomes and results to be materially different from those predicted. The forward-looking statements reflect knowledge and information available at the date of preparation of this
document and the Group undertakes no obligation to update these forward-looking statements. The Group identifies the forward-looking statements by using the words
'anticipates', 'believes', 'expects', 'intends' and similar expressions in such statements. Important factors that could cause actual results to differ materially from those contained in
forward-looking statements, certain of which are beyond the Group’s control, include, among other things: the risk of failure or delay in delivery of pipeline or launch of new
medicines; the risk of failure to meet regulatory or ethical requirements for medicine development or approval; the risk of failure to obtain, defend and enforce effective IP
protection and IP challenges by third parties; the impact of competitive pressures including expiry or loss of IP rights, and generic competition; the impact of price controls and
reductions; the impact of economic, regulatory and political pressures; the impact of uncertainty and volatility in relation to the UK’s exit from the EU; the risk of failures or delays in
the quality or execution of the Group’s commercial strategies; the risk of failure to maintain supply of compliant, quality medicines; the risk of illegal trade in the Group’s medicines;
the impact of reliance on third-party goods and services; the risk of failure in information technology, data protection or cybercrime; the risk of failure of critical processes; any
expected gains from productivity initiatives are uncertain; the risk of failure to attract, develop, engage and retain a diverse, talented and capable workforce; the risk of failure to
adhere to applicable laws, rules and regulations; the risk of the safety and efficacy of marketed medicines being questioned; the risk of adverse outcome of litigation and/or
governmental investigations; the risk of failure to adhere to increasingly stringent anti-bribery and anti-corruption legislation; the risk of failure to achieve strategic plans or meet
targets or expectations; the risk of failure in financial control or the occurrence of fraud; the risk of unexpected deterioration in the Group’s financial position; and the impact that
the COVID-19 global pandemic may have or continue to have on these risks, on the Group’s ability to continue to mitigate these risks, and on the Group’s operations, financial results
or financial condition. Nothing in this document, or any related presentation/webcast, should be construed as a profit forecast.
2
4. Cristian Massacesi
Speakers
4
Chief Oncology Development
Officer and Chief Medical Officer
(for Q&A)
Dr Aleix Prat
Senior Investigator, DESTINY-
Breast04 trial and Head Medical
Oncology, Hospital Clínic of
Barcelona
David Fredrickson
Executive Vice President,
Oncology Business
Pascal Soriot
Chief Executive Officer
Mika Sovak
Vice President and Global
Franchise Head Enhertu, R&D
(for Q&A)
Susan Galbraith
Executive Vice President,
Oncology R&D
Sunil Verma
Senior Vice President, Oncology
Medical (for Q&A)
Andy Barnett
VP, Head of Investor Relations
5. 5
AstraZeneca @ ASCO 2022
Pascal Soriot
Enhertu: the story so far
Susan Galbraith
Enhertu DESTINY-Breast04 trial
Dr Aleix Prat
DESTINY-Breast04: redefining cancer treatment
Dave Fredrickson
What’s next for AZ in Oncology?
Susan Galbraith
1
2
3
4
5
Agenda
Q&A
6
6. AstraZeneca: Oncology 2025+
Innovative
early-stage R&D
6 NME = new molecular entity; LCM = life-cycle management; SoC = standard of care; ADC = antibody-drug conjugate; PROTAC = Proteolysis-targeting chimera; Dato-DXd = datopotamab deruxtecan; CLDN18.2 = isoform 2 of tight
junction protein claudin-18; LoE = loss of exclusivity.
Broad
late-stage pipeline
Strategic business
development
Robust LCM and
LoE profile
Continued investment in
clinical stage pipeline
7 Oncology NMEs
in Phase III
>90 Oncology NME or
major LCM
projects in Phase II and III
Across a number of areas of high
unmet need, with first or best in
class potential
Supplementing the pipeline
with smart deal making
• Enhertu & Dato-DXd
(Daiichi Sankyo)
• CLDN18.2
(Harbour Biomed)
• Longitudinal health data
(Tempus)
• Companion diagnostics
(GRAIL)
Delivering growth through innovation
US LoE for selected medicines
Using precision approaches
and new modalities to create
new SoCs and move earlier
• ADCs, bispecifics, PROTACs,
cell therapy including T-cell
engagers
• Orthogonal combinations
• Digital health
• Multi-omics led research
7. 7
• One plenary presentation
• 9 oral presentations
• 15 poster discussions
• 71 posters
• 12 abstracts (publication
only)
Data
highlights
• Enhertu in breast cancer
DESTINY-Breast04
• Calquence in CLL
Five-year follow up from
ASCEND and ELEVATE-TN
• MEDI5752 in RCC
First results from Phase I
trial
• Lynparza in prostate cancer
Additional safety data from
PROpel
108 abstracts with
96 presentations
4 years of Plenary
Presentations
2019
POLO
2020
ADAURA
2021
OlympiA
2022
DESTINY-
Breast04
CLL = chronic lymphocytic leukaemia; RCC = renal cell carcinoma.
8. 2. Enhertu: the story so far
Susan Galbraith
EVP Oncology R&D
9. Enhertu: best-in-class HER2-directed antibody drug conjugate
9
HER2-positive = human epidermal growth factor receptor 2 positive; T-DXd = trastuzumab deruxtecan (Enhertu); DXd = deruxtecan; TOP1i = topoisomerase I inhibition; ADCC = antibody dependent cell-mediated cytotoxicity; DC =
dendritic cell; CTL = cytotoxic T lymphocyte; Th1 = T-cell helper 1; NK = natural killer cell; CXCL9, 10 = chemokine (CXC motif) ligand 9 and ligand 10; CCL5 = chemokine (CC motif) ligand 5; IL2 = interleukin 2; IFNs = interferons; IFN =
interferon gamma; SoC = standard of care; HR+ = hormone-receptor positive; HR- = hormone-receptor negative; IO = immuno-oncology; DDR = DNA damage response.
9
Enhertu binding
1
TOP1i/DXd
activity
3
Internalisation
2
Target intensity/
density/clustering
DXd release
and entry in
surrounding cells
Immune cell
activation and
recruitment
Bystander
activity
ADCC
Immunogenic
cell death
Lysosomal trafficking
and DXd release
❑ Improve on established HER2+ SoC in
metastatic breast cancer
❑ Expand to multiple HER2-targetable
tumour types
❑ Redefine breast cancer classification –
new HER2-low segment in HR+/-
✓
✓
✓
❑ Improve on established HER2+ SoC in
metastatic breast cancer
❑ Expand to multiple HER2-targetable
tumour types
❑ Redefine breast cancer classification –
new HER2-low segment in HR+/-
❑ Improve long term survival and cure
rate in early stage HER2+/low disease
❑ Orthogonal combinations including IO
and DDR
Achieved
Ongoing
10. neo-adjuvant 1st-line metastatic 2nd-line metastatic 3rd-line metastatic
HER2-positive
breast cancer
neo-adjuvant
replace
chemo +
trastuzumab +
pertuzumab
post neo-adjuvant
replace
T-DM1
replace
chemotherapy +
trastuzumab + pertuzumab
replace
T-DM1 and other standard of care
HER2-low
breast cancer
HR+: neo/adjuvant chemotherapy ±
endocrine therapy
endocrine ± CDK4/6i
replace
chemotherapy and/or endocrine combinations1
HR-: neo/adjuvant chemotherapy +/- IO
replace chemotherapy, evaluate combinations, redefine
TNBC
Beyond
breast cancer
broaden in gastric cancer and expand into NSCLC, CRC and other HER2-expressing cancers
Enhertu has demonstrated efficacy across multiple cancer types
1. Ineligible to endocrine therapy and in those who are endocrine refractory/resistant. HER2-positive = human epidermal growth factor receptor 2 positive; HER2-low = human epidermal growth factor receptor 2 low; HR+ =
hormone-receptor positive; HR- = hormone-receptor negative; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; T-DM1 = trastuzumab emtansine; IO = immuno-oncology; TNBC = triple negative breast cancer; NSCLC = non-small cell
lung cancer; CRC = colorectal cancer.
Leading data in breast and expanding into gastric, lung and colorectal
10
11. Enhertu: potential for activity across spectrum of HER2 expression
11
Sources: AstraZeneca data on file; Tarantino P, et al. J Clin Oncol. 2020; Schettini F, et al. NPJ Breast Cancer. 2021; Owens et al., Clinical Breast Cancer 2004; Lambein et al., American Journal of Clinical Pathology 2013, CAncerMPACT
(2017); Schettini et al. ESMO BC 2020; Nuciforo et al., Molec Onc. 10, 2016; Scott et al. ASCO 2021 Abstract #1021.
HER2 = human epidermal growth factor receptor 2; IHC = immunohistochemistry.
HER2-low
around 50%
HER2-positive
around 20%
HER2-null
potentially 5-20%
HER2-ultralow
potentially 15-30%
HER2-positive breast cancer, IHC 3+
HER2-positive breast cancer, IHC 3+
HER2-positive breast cancer, IHC 3+
HER2-null breast cancer
IHC 0: ~20k receptors
per cell
HER2-positive breast cancer
IHC 3+: ~2 million HER2
receptors per cell
HER2-low breast cancer
IHC 2+: ~200k-500k HER2 receptors
per cell
IHC 1+: ~100k-200k HER2 receptors
per cell
HER2-ultralow breast cancer
IHC >0 and <1+: ~20k-100k
receptors per cell
HER2-expression
split in breast
cancer
3+
2+ 1+
0
0+
<1
12. Results from the J101 Phase I trial paved the way for Enhertu in
HER2-low breast cancer
12
Best percentage change in sum
of target lesion size from
baseline by IHC status
Percentage change in
sum of target lesion size from
baseline by IHC status
Source: Modi et al., SABCS 2018, Poster # P6-17-02.
HER2-low = human epidermal growth factor receptor 2 low; IHC = immunohistochemistry; HR- = hormone-receptor negative; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ORR = objective response rate; mDOR = median
duration of response; mPFS = median progression-free survival.
Safety in HER2-low breast cancer
was consistent with other
Enhertu breast cancer trials
Promising antitumor activity
seen in heavily pretreated
HER2-low patients
Efficacy seen in
post-CDK4/6 inhibitors
and IHC 1+ subgroups
ORR: 44.2% | mDOR: 8.1m | mPFS 7.6m
13. 3. Enhertu Phase III
DESTINY-Breast04 trial
Dr Aleix Prat
Senior Investigator, DESTINY-
Breast04 trial, and Head
Medical Oncology, Hospital
Clínic of Barcelona
14. DESTINY-Breast04 trial design
14
T-DXd = trastuzumab deruxtecan; HER2 = human epidermal growth factor receptor 2; HER2-low = human epidermal growth factor receptor 2 low; IHC = immunohistochemistry; ISH = in situ hybridization; mBC = metastatic breast cancer; HR+ = hormone-receptor
positive; R = randomised; Q3W = every three weeks; TPC = treatment of physician’s choice; PFS = progression-free survival; BICR = blinded independent central review; OS = overall survival; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor.
aIf patients had HR+ mBC, prior endocrine therapy was required. bPerformed on adequate archived or recent tumor biopsy per ASCO/CAP guidelines using the VENTANA HER2/neu (4B5) investigational use only [IUO] Assay system. cTPC was administered accordingly
to the label. dOther secondary endpoints included ORR (BICR and investigator), DOR (BICR), PFS (investigator), and safety; efficacy in the HR− cohort was an exploratory endpoint.
First randomised Phase III trial of T-DXd for HER2-low mBC - An open label,
multicenter trial
Primary endpoint
• PFS by BICR (HR+)
Key secondary endpointsd
• PFS by BICR (all patients)
• OS (HR+ and all patients)
R
2:1
Patientsa
• HER2-low (IHC 1+ vs IHC
2+/ISH−), unresectable, and/or
mBC treated with 1-2 prior lines
of chemotherapy in the
metastatic setting
• HR+ disease considered
endocrine refractory
T-DXd
5.4 mg/kg Q3W
(n = 373)
TPC
Capecitabine, eribulin,
gemcitabine, paclitaxel,
nab-paclitaxelc
(n = 184)
HR+ ≈ 480
HR− ≈ 60
Stratification factors
• Centrally assessed HER2 statusb (IHC 1+ vs IHC 2+/ISH−)
• 1 vs 2 prior lines of chemotherapy
• HR+ (with vs without prior treatment with CDK4/6 inhibitor) vs HR−
15. Baseline characteristics
15 HER2 = human epidermal growth factor receptor 2; IHC = immunohistochemistry; ISH = in situ hybridization; ECOG = Eastern Cooperative Oncology Group; T-DXd = trastuzumab deruxtecan; TPC = treatment of physician’s choice.
aHormone receptor status is based on data collected using the interactive web/voice response system at the time of randomization, which includes mis-stratified patients.
Hormone receptor-positive All patients
T-DXd
(n = 331)
TPC
(n = 163)
T-DXd
(n = 373)
TPC
(n = 184)
Age, median (range), years 57 (32-80) 56 (28-80) 58 (32-80) 56 (28-80)
Female, n (%) 329 (99) 163 (100) 371 (99) 184 (100)
Region, n (%)
Europe + Israel 149 (45) 73 (45) 166 (45) 85 (46)
Asia 128 (39) 60 (37) 147 (39) 66 (36)
North America 54 (16) 30 (18) 60 (16) 33 (18)
HER2 status (IHC), n (%)
1+ 193 (58) 95 (58) 215 (58) 106 (58)
2+/ISH− 138 (42) 68 (42) 158 (42) 78 (42)
ECOG performance status, %
0
187 (56) 95 (58) 200 (54) 105 (57)
1 144 (44) 68 (42) 173 (46) 79 (43)
Hormone receptora, n (%)
Positive
328 (99) 162 (99) 333 (89) 166 (90)
Negative 3 (1) 1 (1) 40 (11) 18 (10)
Brain metastases at baseline, n (%) 18 (5) 7 (4) 24 (6) 8 (4)
Liver metastases at baseline, n (%) 247 (75) 116 (71) 266 (71) 123 (67)
Lung metastases at baseline, n (%) 98 (30) 58 (36) 120 (32) 63 (34)
16. Prior therapies
16
CDK4/6 = cyclin-dependent kinase 4/6; T-DXd = trastuzumab deruxtecan; TPC = treatment of physician’s choice.
Hormone receptor-positive All patients
T-DXd
(n = 331)
TPC
(n = 163)
T-DXd
(n = 373)
TPC
(n = 184)
Lines of systemic therapy (metastatic setting)
Median number of lines (range) 3 (1-9) 3 (1-8) 3 (1-9) 3 (1-8)
Number of lines, n (%)
1 23 (7) 14 (9) 39 (10) 19 (10)
2 85 (26) 41 (25) 100 (27) 53 (29)
≥3 223 (67) 108 (66) 234 (63) 112 (61)
Lines of chemotherapy (metastatic setting)
Median number of lines (range) 1 (0-3) 1 (0-2) 1 (0-3) 1 (0-2)
Number of lines, n (%)
0 1 (0.3) 1 (0.6) 1 (0.3) 1 (0.5)
1 203 (61.3) 93 (57.1) 221 (59.2) 100 (54.3)
2 124 (37.5) 69 (42.3) 145 (38.9) 83 (45.1)
≥3 3 (0.9) 0 6 (1.6) 0
Lines of endocrine therapy (metastatic setting)
Median number of lines (range) 2 (0-7) 2 (0-6) 2 (0-7) 2 (0-6)
Number of lines, n (%)
0 28 (8) 17 (10) 60 (16) 34 (18)
1 105 (32) 49 (30) 108 (29) 51 (28)
2 110 (33) 53 (33) 115 (31) 54 (29)
≥3 88 (27) 44 (27) 90 (24) 45 (24)
Prior targeted cancer therapy, n (%)
Targeted therapy 259 (78) 132 (81) 279 (75) 140 (76)
CDK4/6 inhibitor 233 (70) 115 (71) 239 (64) 119 (65)
19. PFS subgroup analysis in HR+ cohort
19
PFS by blinded independent central review. Based on derived data, which includes protocol deviations.
CDK4/6 = cyclin-dependent kinase 4/6; IHC = immunohistochemistry; ISH = in situ hybridization; ECOG = Eastern Cooperative Oncology Group; T-DXd = trastuzumab deruxtecan; TPC = treatment with physician’s choice; mPFS =
median progression-free survival; CI = confidence interval.
20. Safety and tolerability
20
TEAE = treatment-emergent adverse event; T-DXd = trastuzumab deruxtecan; TPC = treatment with physician’s choice; ILD = interstitial lung disease.
aPatient years of exposure are the treatment duration with year as unit. bGrouped term. cFatigue includes the preferred terms fatigue, malaise and asthenia; neutropenia included the preferred terms of neutropenia and neutrophil
count decreased. dOn-treatment death was defined as any death that occurred from the date of the first dose to 47 days after the last dose of study drug irrespective of the cause, the TEAEs associated with deaths represent subset
of on-treatment deaths reported by the investigators as adverse events.
• Median treatment duration
– T-DXd: 8.2 months (range, 0.2-33.3)
– TPC: 3.5 months (range, 0.3-17.6)
• Most common TEAE associated with treatment
discontinuation
– T-DXd: 8.2%, ILD/pneumonitisb
– TPC: 2.3%, peripheral sensory neuropathy
• Most common TEAE associated with dose reduction
– T-DXd: 4.6%, nausea and fatigue
– TPC: 14.0%, neutropeniac
• T-DXd drug related ILD/pneumonitis AEs
– Grade 3: 8 (2.1%)
– Grade 5: 3 (0.8%)
• Total on-treatment deathsd
– T-DXd: 3.8%
– TPC: 4.7%
Safety analysis set
n (%)
T-DXd
(n = 371)
TPC
(n = 172)
Total patient-years of exposure, yearsa 283.55 63.59
TEAEs
Grade ≥3
369 (99)
195 (53)
169 (98)
116 (67)
Serious TEAEs 103 (28) 43 (25)
TEAEs associated with dose discontinuations 60 (16) 14 (8)
TEAEs associated with dose interruptions 143 (39) 72 (42)
TEAEs associated with dose reductions 84 (23) 66 (38)
TEAEs associated with deaths 14 (4) 5 (3)
21. DESTINY-Breast04 establishes T-DXd as the new
standard of care in HER2-low, HR+/HR- mBC
21 T-DXd = trastuzumab deruxtecan; HER2-low = human epidermal growth factor receptor 2 low; HR+ = hormone-receptor positive; HR- = hormone-receptor negative; mBC = metastatic breast cancer; PFS = progression-free survival;
OS = overall survival; TPC = treatment with physician’s choice; IHC = immunohistochemistry; CDK4/6i = cyclin-dependent kinase 4/6 inhibitors.
• T-DXd is the first HER2-targeted therapy to
demonstrate unprecedented statistically significant
and clinically meaningful improvement in PFS and OS
versus TPC
• Similar magnitude of benefit across all subgroups,
including HER2 IHC status and prior CDK4/6i use
• Safety is consistent with the known safety profile and
showed an overall positive benefit-risk
• DESTINY-Breast04 establishes HER2-low (IHC 1+, IHC
2+/ISH−) mBC as a new targetable patient population
with T-DXd as a new standard of care
Hazard ratio: 0.50, P <0.0001
Progression-free Survival
Hazard ratio: 0.64, P = 0.001
Overall Survival
5.1 mo
9.9 mo
T-DXd
TPC
Median
23.4 mo
16.8 mo
T-DXd
TPC
Median
Efficacy in All Patients
(HR+ and HR−)
23. Enhertu: continuing to transform breast cancer
23
2019: DESTINY-Breast011 2021: DESTINY-Breast032 2022: DESTINY-Breast04
1. Krop SABCS 2019 Abstract #GS1-03. 2. Cortes ESMO 2021 Abstract #LBA1
HER2 = human epidermal growth factor receptor 2; T-DXd = trastuzumab deruxtecan; TPC = treatment of physician’s choice; mPFS = median progression-free survival.
…to redefining expectations in 2nd
line HER2-positive breast cancer…
…to now reaching more than half
of all breast cancer patients
From compelling Phase II data in 3rd
line+ HER2-positive breast cancer…
mPFS 9.9m
mPFS: 16.4m
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
T-Dxd (261) 261 256 250 244 240 224 214 202 200 183 168 164 150 132 112 105 79 64 53 45 36 29 25 19 10 6 5 3 2 0 0 0 0
T-DM1 (263) 263 252 200 163 155 132 108 96 93 78 65 60 51 43 37 34 29 23 21 16 12 8 6 4 1 1 1 1 1 1 1 1 0
Progression-Free
Survival
probability,
%
Time, months
Patients Still at Risk:
Censor
T-DXd (n = 261)
T-DM1 (n = 263)
T-DXd
Probability
of
Progression-Free
Survival
Months
1.0
0.8
0.6
0.4
0.2
0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 20
16 17 18 19
184 182 174 155 153 135 121 107 103 94 69 54 38 17 11 10 0
9 4 3 1
No. at risk:
Censored: 68.5%
Events: 31.5%
mPFS: not reached
24. HER2-low breast cancer:
visible, but underserved
24
1. AstraZeneca data on file. 2. NIH NCI SEER data.
HR+ = Hormone receptor positive (cancer that is driven by oestrogen and/or progesterone) . TNBC = triple negative breast cancer is both HR- and HER2-. CDK4/6i
Cyclin-dependent kinase 4,6 inhibitors such as palbociclib, target the mechanisms of uncontrolled growth of HR+ cancer cells. Endocrine therapies target the
hormones that drive HR+ cancer and include SoC SERDs Faslodex (fulvestrant) and aromatase inhibitors like Arimidex (anastrozole)
~12% 5-year survival for metastatic,
triple negative breast cancer in the US2
~32% 5-year survival for metastatic,
HR+ breast cancer in the US2
Outcomes are currently poor
Patients are numerous
and ready to be identified
HER2+
HER2-low/HR-
HER2-low/HR+
HER2-ultralow
~90%+ of
breast
cancer
~20% of
breast
cancer
Detailed
characterisation
of HER2 status
must become
standard
procedure
25. Enhertu transforms the treatment paradigm
25
1. Sledge GW. et al., JAMA Oncol 2020.6(1) 116-124. 2. Giridhar GV., SABCS 2018 Abstract #P6-18-09. 3. Chainitikun S. et al., Breast Cancer Research and Treatment 2020. 4. Rossi L et al., Breast Cancer Res 21, 71(2019). 5. Turner NC. Et al., 2018 Nov 15,379(30) 1925-
1936. 6. Xi j. et al., JNCCN 2019.
HR+ = hormone-receptor positive; RWE = real-world evidence; ET = endocrine therapy; CDK4/6i = cyclin-dependent kinase 4/6 inhibitors; MDACC = MD Anderson Cancer Center.
for HR+ metastatic patients who see limited benefit from current standards of care
2L+ 3.4m to 4.4m
2L+ 3.1m
3L+
3L+
chemotherapy
MONARCH-2: post treatment1,
Mayo Clinic RWE study2,
MDACC RWE study3
ET monotherapy
Mayo Clinic RWE study
chemotherapy
Mayo Clinic RWE study, TREnd post
treatment4, PALOMA-3 post treatment5,
Siteman Cancer Centre RWE study6
ET monotherapy
Mayo Clinic RWE study, TREnd post treatment, PALOMA-3 post
treatment, Siteman Cancer Centre RWE study
2.6m to 4.8m
3.7m to 5.6m
Enhertu
DESTINY-Breast04 - HR+ post CDK4/6i cohort
3L+ 10.0m
4L+
sacituzumab govitecan
TROPICS-02 trial 5.5m
26. Establishing a new standard of care
Enhertu set to deliver greater benefit than all
current therapies beyond second line
Source: AstraZeneca data on file.
HR+ = hormone-receptor positive; ET = endocrine therapy; CDK4/6i = cyclin-dependent kinase 4/6 inhibitors.
1st line 2nd line 5th line
4th line
3rd line
ET monotherapy
ET + CDK4/6
inhibitors
Other ET
combinations
1st chemotherapy
2nd chemotherapy
Other therapies
-Breast04
-Breast06
-Breast04
-Breast06
-Breast04
-Breast06
-Breast06
~60k HR+ patients in US, EU and Japan
27. 5. What’s next for
AstraZeneca in Oncology?
Susan Galbraith
EVP Oncology R&D
28. Dato-DXd could address “triple negative” patients
28
TROPION-Breast02
TROP2 targeting in order to redefine TNBC
BEGONIA Arm 7
(Dato-DXd + Imfinzi)
Source: Schmid ESMO Breast 2022, Abstract #166MO.
Dato-DXd = datopotamab deruxtecan; HER2-negative = human epidermal growth factor receptor 2 negative; HR- = hormone-receptor negative; PD-L1 = programmed death-ligand 1; ORR = objective response rate; CI = confidence
interval; TROP2 = trophoblast antigen 2; TNBC = triple negative breast cancer; mBC = metastatic breast cancer; PD-1 = programmed cell death protein 1; ECOG = Eastern Cooperative Oncology Group; PS = performance status; PFS =
progression-free survival; OS = overall survival; DoR = duration of response.
TROPION-Breast02 Phase III in HER2-negative/HR-negative breast cancer
Key eligibility criteria:
• Locally recurrent inoperable or metastatic TNBC
• No prior chemo or targeted systemic therapy for
mBC
• Not a candidate for PD-1 / PD-L1 inhibitor therapy
• Measurable disease as defined by RECIST v1.1
• ECOG PS 0 or 1
Dato-DXd
Investigators’ choice
of chemotherapy
Dual primary endpoints:
PFS (BICR) and OS
Secondary endpoints:
PFS (inv), ORR, DoR, safety
n=300
1:1 randomisation
n=300
Data
readout:
>2023
HER2-low/HER2-null tumour cells could have around
five times more TROP2 receptors per cell versus HER2
ORR% (CI): 74% (51% - 89%)
29. Early 1st line 2nd line 3rd line 3rd line+
HER2+ HER2-high
~20% of patients
Hormone-receptor
positive (HR+),
HER2-negative
HER2-low/ultralow,
TROP2+, ET
sensitive/resistant, DDR
targetable
~65% of patients
TNBC ~15% of patients
HR- HER2-low, TROP2+, IO,
DDR targetable
Positioned to address the full spectrum of breast cancer
29
Illustrative settings and populations. Not to scale. Includes planned trials.
HER2 = human epidermal growth factor receptor 2; HER2-low = human epidermal growth factor receptor 2 low; HR+ = hormone-receptor positive; HR- = hormone-receptor negative; TNBC = triple negative breast cancer; TROP2+ = trophoblast
antigen 2 positive; IO = immuno-oncology; DDR = DNA damage response; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ET = endocrine therapy; HRD+ = homologous recombination deficiency positive; ADC = antibody-drug conjugate; THP =
paclitaxel , trastuzumab and pertuzumab; T-DM1 = trastuzumab emtansine; AI = aromatase inhibitor.
with potential for at least seven medicines in monotherapy and combinations
HRD+, HR+/-
HR+,
ET sensitive
HER2-low, HR+,
ET resistant
HER2+ HER2+
HR+,
HER2-low/
ultralow
HR+/-,
HER2-low
TROP2+,
HER2-null
HR-, HER2-low
Enhertu + potential combinations
-displace T-DM1, chemotherapy
Enhertu + potential
combinations
-displace THP
HR+, ET
sensitive
capivasertib
+
potential
combos
-displace
everolimus,
alpelisib
Dato-DXd + potential combos
-displace chemotherapy
Dato-DXd
+ potential combinations
-displace
chemotherapy
Enhertu
-displace late line
ET, chemotherapy
Enhertu
Enhertu
camizestrant + CDK4/6i
-displace fulvestrant/AI, move earlier
Lynparza, AZD5305 + potential combinations
ADC +/- IO + potential combinations
capivasertib
+ potential combinations
HER2-low
~50% of
patients
TROP2+, HER2-null, HR-
HER2-low/null, HR-
Enhertu
-displace late line
ET, chemotherapy
Dato-DXd + potential combinations
-displace chemotherapy
30. Dato-DXd: initial TROP2 opportunities
30 NSCLC = non-small cell lung cancer; AGA = actionable genomic alterations; HR+ = hormone-receptor positive; HER2-negative = human epidermal growth factor receptor 2 negative; SBRT = stereotactic body radiotherapy; CRT =
chemoradiation therapy; IO = immuno-oncology; DDR = DNA damage response; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor.
Resectable Unresectable Metastatic
Stage IA
Stage IB -
III
Stage I-II Stage III 1st line 2nd line+
Without AGA Surgery
Chemo-
therapy
SBRT CRT -> IO TROPION-Lung08 TROPION-Lung01
With AGA Surgery
Tyrosine
kinase
inhibitors
SBRT Tyronise kinase inhibitors Tyrosine kinase inhibitors TROPION-Lung05
Neoadjuvant and adjuvant 1st line 2nd line 3rd line
HR+
Chemotherapy
+/- endocrine therapy, DDR
Endocrine therapy +/- CDK4/6i TROPION-Breast01
HR-, HER2-
negative
Chemotherapy +/- IO, DDR BEGONIA/TROPION-Breast02 J101 J101
Breast
cancer
NSCLC
At least five new Phase III trials planned to commence in the next 18 months
31. Updated overall survival data from Phase II trial that supported CAPItello-291
31
AKT = protein kinase B; OS = overall survival; HR = hazard ratio; ER+ = oestrogen receptor positive; BC = breast cancer; ET = endocrine therapy; PFS = progression-free survival; PI3K = phosphoinositide 3-kinase.
Key eligibility criteria:
• post-menopausal women with metastatic ER+ BC
• suitable for ET.
• < three lines of prior ET and up to one line of chemo
in metastatic setting
• Progressive disease during treatment with an
aromatase inhibitor
capivasertib +
fulvestrant
Placebo +
fulvestrant
Primary endpoint:
PFS
n=350
1:1 randomisation
n=350
Capivasertib: oral, potent and selective pan-AKT inhibitor
CAPItello-291 Phase III trial
FAKTION Phase II trial
Targeting the PI3K/AKT pathway as a common
mechanism of resistance to endocrine therapy
Fulvestrant +
placebo
Fulvestrant +
capivasertib
Fulvestrant + capivasertib (n = 69) Fulvestrant + placebo (n = 71)
OS events 49 59
Median OS
(95% CI)
29.3 months (23.7–39.0) 23.4 months (18.7–32.7)
Adjusted
HR 0.66 (95% CI 0.45–0.97); p = 0.035
32. AZD8205: ADC targeting B7-H4 protein
From histology to histogram:
quantitative continuous score-based
image analysis for B7-H4
Encouraging preclinical efficacy
and PARPi-selective combination data
Kinneer et al AACR. Wortmann P, et al. “Development and implementation of image analysis-based Quantitative Continuous Score (QCS) for B7-H4 IHC to understand AZD8205 pharmacodynamics”. AACR 2022; Abstract 452/3.
ADC = antibody-drug conjugate; B7-H4 = immune co-regulatory ligand of the B7 family; AI = artificial intelligence; OD = once daily; PARPi = poly ADP ribose polymerase inhibitor; ORR = objective response rate; TGI = tumour growth inhibition; TNBC = triple
negative breast cancer; PDX = patient-derived xenografts; QDx28 = every 28 days; SD = single dose.
The first ADC engineered with AstraZeneca’s novel linker-warhead technology
A: AI-based identification
of tumour epithelial region
and segmentation into
cells
C: Mean target expression per cell
membrane/cytosol is analysed at
whole slide image level
B: Target expression quantified for
nucleus, cytosol and membrane from
stain isolation layer based on Hue-
Saturation-Density transform
%
Regression
%TGI
-100
-50
0
50
100
Avg response, 3.5 mg/kg ORR = 69%
Robust efficacy in
vivo of 26 TNBC PDX
tumours
Significant
combination benefit
seen in preclinically
with AZD5305
33. MEDI5752: a novel PD-1/CTLA-4 bispecific
Potential for improved therapeutic index versus components
33
Durable clinical response in Phase I trial
Deep responses seen across
a range of tumours
PD-1 = programmed cell death protein 1; CTLA-4 = cytotoxic T-lymphocyte–associated antigen 4; mDOR = median duration of response; CI = confidence interval; RCC = renal cell carcinoma; TNBC = triple negative breast cancer; PD-
L1-low = programmed death-ligand 1 low; NSCLC = non-small cell lung cancer.
mDOR: 17.5 months (95% CI: 5.7 – NE)
Best
change
in
target
lesion
burden
(%)
-100
-75
-50
-30
0
20
50
75
100
2.25 mg
500 mg
7.5 mg
750 mg
22.5 mg
1500 mg
75 mg
2000 mg
225 mg
2500 mg
including RCC, TNBC, PDL1-low NSCLC,
gastric, bladder and colorectal cancer
34. MEDI5752 in advanced renal cell carcinoma
Deep and durable responses in immunotherapy-naïve patients
34
1500 mg dose expansion
responses
Change from baseline (%)
750 mg dose expansion
responses
Change from baseline (%)
Emerging efficacy at 750mg
looks similar to 1500mg
monotherapy
Source: Tran et al., AACR 2022, Abstract #CT016
IO = immuno-oncology; RCC = renal cell carcinoma; Q3W = every three weeks; DoR = duration of response; PFS = progression-free survival; CI = confidence interval.
750mg 1500mg 2000mg 2500mg
Median DoR, months (95% CI) 16.2 (4.1–NE)
Median PFS, months (95% CI) 16.1 (4.6–NE)
Median duration of follow-up,
months (range)
18.4 (0.5-23.6)
Median DoR, months (95% CI) Data immature
Median PFS, months (95% CI) Data immature
Median duration of follow-up,
months (range)
6.9 (1.4-10.9)
Improved toxicity, fewer treatment
discontinuations and similar efficacy for
750mg dose compared to higher dose
100
80
60
40
20
0
-20
-40
-60
-80
-100
0 2 4 6 8 10
Time (months) n=27
100
80
60
40
20
0
-20
-40
-60
-80
-100
0 2 4 6 8 10 12 14 16 18 20 22
Time (months) n=12
Across all cohorts in 1st line RCC:
ORR 51% (25/49)
35. Calquence: best-in-class BTK inhibitor
Superior, durable efficacy and tolerability profile supports long-term use
35
ASCEND
relapsed/refractory CLL
ELEVATE-TN
treatment naïve CLL
Calquence sees 62% PFS benefit at four years
Calquence + obintuzumab sees strong 84%PFS
benefit at five years
37. Cristian Massacesi
Panel
37
Chief Oncology Development
Officer and Chief Medical Officer
(for Q&A)
Dr Aleix Prat
Senior Investigator, DESTINY-
Breast04 trial and Head Medical
Oncology, Hospital Clínic of
Barcelona
David Fredrickson
Executive Vice President,
Oncology Business
Pascal Soriot
Chief Executive Officer
Mika Sovak
Vice President and Global
Franchise Head Enhertu, R&D
(for Q&A)
Susan Galbraith
Executive Vice President,
Oncology R&D
Sunil Verma
Senior Vice President, Oncology
Medical (for Q&A)
40. Confirmed objective response rate
40
Hormone receptor status is based on data from the electronic data capture corrected for misstratification.
ORR, objective response rate; T-DXd, trastuzumab deruxtecan; TPC, treatment of physician’s choice.
aThe response of 1 patient was not confirmed. bClinical benefit rate is defined as the sum of complete response rate, partial response rate, and more than 6 months’ stable disease rate, based on blinded independent central review.
0
10
20
30
40
50
60
Percentage
3.6
Progressive disease, %
Not evaluable, %
Clinical benefit rate,b %
Duration of response, months
7.8 21.1 12.5 33.3
4.2 12.7 7.5 5.6
71.2 34.3 62.5 27.8
10.7 6.8 8.6 4.9
Complete Response
Partial Response
Hormone receptor–positive Hormone receptor–negative
T-DXd (n = 333) T-DXd (n = 40)
TPC (n = 166) TPC (n = 18)
Confirmed Objective Response Rate
52.6%a
50.0%
16.3% 16.7%
49.2 47.5
2.5
0.6
15.7
5.6
11.1
41. Best change in target lesions (all patients)
41
Shown are the best percentage changes from baseline in the sum of the largest diameters of measurable tumors in patients for whom data from both baseline and postbaseline assessments of target lesions by independent
central review were available. The upper dashed horizontal line indicates a 20% increase in tumor size in the patients who had disease progression, and the lower dashed line indicates a 30% decrease in tumor size (partial
response).
HR, hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridization; T-DXd, trastuzumab deruxtecan; TPC, treatment of physician’s choice.
41
Best
%
Change
in
Sum
of
Diameters
From
Baseline
* *
*
*
*
*
**
*
**
*
*
**
*
*
*
*
-100
-80
-60
-40
-20
0
20
40
60
80
100
IHC 1+
IHC 2+/ISH−
*Patients with HR− disease
IHC 1+
IHC 2+/ISH−
0
*
*
* *
**
*
*
*
***
*
* *
*
*
*
*
*
**
**
***
*
* *
*
*
* *
-100
-80
-60
-40
-20
0
20
40
60
80
100
T-DXd (n = 348) TPC (n = 156)
43. Use of AstraZeneca slides from conference calls and webcasts
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