METASTATIC BREAST CANCER

Size: px

Start display at page:

Download "METASTATIC BREAST CANCER"

Homer Beasley
5 years ago
Views:

Preferences: From Trials to Translation A Year 2013 Update William J.

Program Chicago, Illinois Question # 1: What are the unresolved issues in improving alignment of available therapies with the heterogeneous population of patients with MBC?

What are your decision triggers, considerations, and pivot points when you formulate your treatment regimens for specific patient subsets?

2 Click Here to View at: The iq&a interactive Medical Intelligence Zone for METASTATIC BREAST CANCER Focus on Evidence-Based Treatment for Survival Prolongation Based on Receptor Status, Clinical Profiles and Patient Preferences: From Trials to Translation A Year 2013 Update William J. Gradishar, MD Division of Hematology and Medical Oncology Feinberg School of Medicine at Northwestern University Director of Breast Medical Oncology Associate Director, Lynn Sage Comprehensive Breast Program Chicago, Illinois Question # 1: What are the unresolved issues in improving alignment of available therapies with the heterogeneous population of patients with MBC? Is there a standard approach? Question # 2: How do you conceptualize your non-prescriptive treatment algorithms for patients with MBC? What are your decision triggers, considerations, and pivot points when you formulate your treatment regimens for specific patient subsets? Question # 3: How do you formulate your chemotherapy-based treatment regimens for patients who are no longer candidates for endocrine therapy or who are triple negative? Question # 4: Based on previous results of landmark trials, such as EMBRACE, what in your view was the rationale for constructing the 301 Trial comparing capecitabine and eribulin in early line therapy? And what is your interpretation of the results? Question # 5: In your view does the 301 Trial offer us evidence-based guidance for navigating in the therapeutic white space and unmet need we currently have for triple negative patients with MBC? Question # 6: Can you discuss how the 301 Trial might apply to the patients with MBC at the front lines of practice? And how you might discriminate among treatment options? Question # 7: What are the unanswered questions regarding classification and signaling systems within subsets for triple negative patients with MBC? YOUR QUESTIONS Supported by an educational grant from: Visit us at EXPERT ANSWERS

Linda Vahdat, MD Director, Breast Cancer Research Program Head, Solid Tumor Service Weill Cornell Medical College New York, New York Question # 8: Given the results with eribulin in late line

Question # 9: What was the design of the 301 trial evaluating eribulin in early line settings for breast cancer, and what historical and evidencebased factors informed the specific trial design and

Question # 10: What were the overall survival results observed in the 301 trial, with respect with to pre-specified secondary end points based on biomarkers, including HER2 receptor status and triple

3 Linda Vahdat, MD Director, Breast Cancer Research Program Head, Solid Tumor Service Weill Cornell Medical College New York, New York Question # 8: Given the results with eribulin in late line settings for advanced breast cancer, what was the rationale for conducting the 301 trial? Question # 9: What was the design of the 301 trial evaluating eribulin in early line settings for breast cancer, and what historical and evidencebased factors informed the specific trial design and dosing? Question # 10: What were the overall survival results observed in the 301 trial, with respect with to pre-specified secondary end points based on biomarkers, including HER2 receptor status and triple negative patients? Question # 11: Given the clinical challenges of treating triple negative patients with advanced breast cancer, what in your view are the implications of the results seen in the pre-specified subsets in the 301 trial? Question # 12: Despite failure of 301 to meet its overall survival and PFS primary end points, how might the results seen in biomarker-specific subsets change our clinical approach to certain patient types with MBC? Question # 13: What trial-related information from 301 especially safety results and pre-specified subset analysis can help us refine our sequencing and drug selection approaches for capecitabine and eribulin in MBC? What are the pivot points for these choices? Question # 14: Given the limited and unproven choices for triple negative cohorts in metastatic breast cancer, how in your view does the 301 trial shed light on possible strategies moving forward? Question # 15: What other studies are you presenting at the San Antonio Breast Cancer Meeting in 2012? Debu Tripathy, MD Priscilla and Art Ulene Chair in Women s Cancer Co-Leader, Women s Cancer Program University of Southern California Los Angeles, California Question # 16: What are the new developments in the area of MBC that have been reported at the 2012 San Antonio Breast Meeting? And where does the 301 Trial with eribulin and capecitabine fit in to these advances? Question # 17: Based on your reading of the current landscape for treatment of MBC, where does the 301 Trial comparing eribulin and capecitabine fit into our current thinking for early versus late line treatment choices for MBC? Question # 18: Given that trial-generated signals for how to optimally approach triple negative patients have been in short supply, what do we take from the 301 trial in this regard? Question # 19: Although there are many ways to measure aggressive disease, how should we approach these patients given what we currently know? Question # 20: What new developments in the biology of triple negative breast cancer management were presented at the San Antonio Breast Meeting in December, 2012? Question # 21: What new data and findings related to DNA repair in triple negative breast cancer? Question # 22: What advances in combinatorial therapy do you envision based on the work you are involved with in your lab? Question # 23: What do past and current trials teach us about the roadmap for improving outcomes in triple negative breast cancer? Hope S. Rugo, MD Director, Breast Oncology and Clinical Trials Education UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California Question # 24: What have studies on metastatic breast cancer taught us about how to sequence therapy hormonal, biologics, and chemotherapy for this difficult-to-treat population? Question # 25: From a clinical trial development perspective, how did the results of EMBRACE trial, which evaluated eribulin, establish this agent as a foundation therapy for survival prolongation in MBC? Question # 26: Based on what we learned from the EMBRACE trial, what was the rationale for designing the 301 trial with eribulin according to the parameters and comparators that were used? Question # 27: Can you share your interpretation of the overall efficacy and safety results of the 301 trial and what the important findings are that might impact our practice? Question # 28: What are your take home messages as they relate to the results of the pre-specified end points based on receptor status in subgroups with MBC? Take us to the front lines of practice. Professor Christopher Twelves, MD NTRAC Professor of Clinical Cancer Pharmacology and Oncology Professor and Honorary Consultant in Medical Oncology St. James s University Hospital Leeds, United Kingdom Question # 29: Having been involved in the EMBRACE trials and the clinical trial program for eribulin, what do you feel is the special importance of the 301 Trial in the evolution of our understanding of how to treat MBC? YOUR QUESTIONS EXPERT ANALYSIS

Question # 30: With respect to 301, what was the rationale for the pre-specified subgroup analysis and how might we incorporate these findings into our clinical thinking about late-stage breast

What does the subgroup analysis teach us and what signals does it present for our consideration as far as options for early and later lines of therapy?

4 Question # 30: With respect to 301, what was the rationale for the pre-specified subgroup analysis and how might we incorporate these findings into our clinical thinking about late-stage breast cancer? Question # 31: What is your reading of the results for overall survival in the 301 Trial? What does the subgroup analysis teach us and what signals does it present for our consideration as far as options for early and later lines of therapy? Question # 32: Given that the 301 Trial overall primary end points did not meet statistical significance, what nevertheless is the value of this trial as a guide to clinical decisionmaking for earlier lines of treatment in MBC? Minetta Liu, MD Breast Cancer Specialist Mayo Clinic Rochester, Minnesota Question # 33: Do you subscribe to or advocate a specific sequencing algorithm for treatment of metastatic breast cancer? Question # 34: How do position the anthracyclines, taxanes, capecitabine, and eribulin in your progressive treatment plan for advanced breast cancer? How do you pivot among and sequence these agents? Question # 35: Based on previous results of landmark trials, such as EMBRACE, what in your view was the rationale for constructing the 301 Trial comparing capecitabine and eribulin in early line therapy? Question # 36: What did we learn from the 301 Trial? What did we not learn? What hypothesis-generating results and subsets should we focus on? What can we apply to our breast cancer practice? Question # 37: What were the results in the triple negative subset studied in the 301 Trial and should these findings guide our practice for MBC in this patient group? Question # 38: Based on the data comparing capecitabine and eribulin at the 2012 San Antonio Breast Meeting, can you tell us how you would approach specific cohorts of patients with MBC at the front lines, including those who are triple negative? Question # 39: What, in your view, are the looming questions and issues that we still need to resolve and refine when making treatment decisions for patients with MBC? Stefan Glück, MD, PhD Miller School of Medicine University of Miami Clinical Director, Braman Family Breast Cancer Institute Sylvester Comprehensive Cancer Center Miami, Florida Question # 40: How do we identify and clinically assess patients with MBC who should be treated with microtubule-targeted agents? For early versus late line treatment? Question # 41: How do you suggest we consider, choose among, and sequence the specific microtubule-targeting agents that are approved for early and late line treatment of MBC? Question # 42: What is the current approach to later lines of therapy for patients with MBC? Can you provide us a patient-centric approach to survival extension? Question # 43: How do you select agents for advanced breast cancer based on safety and toxicity consideration? Question # 44: Given the robust range of results and pre-specified subgroups analyzed in the 301 Trial with eribulin and capecitabine, what do you feel are the clinical implications for early and late line therapy based on this study? Question # 45: How do you see the 301 Trial data affecting how we approach patients with triple negative breast cancer (TNBC)? Edith Perez, MD Mayo Medical School Director of the Breast Program Chair of the Cancer Clinical Study Unit Mayo Clinic, Florida Question # 46: How do the results of the 301 Trial allow breast cancer specialists to advance their clinical decision-making for patients with advanced breast cancer? Question # 47: Although the 301 Trial suggests the need for additional investigations, what is it that oncologists can take now and apply to the front line of treatment, especially as it relates to survival improvements? Question # 48: Based on 301, will you change your approach to patients with triple negative disease or other clinical features associated with MBC? Question # 49: What do you see as the most urgent and pressing issues today regarding optimizing treatment for and improving survival in MBC? Question # 50: What new studies, information, and techniques in the area of biomarkers have been reported that might help us make clinical decisions in MBC? YOUR QUESTIONS EXPERT DISCUSSION

Question # 51: How might we meet the challenges of classifying and treating patients with triple negative breast cancer based on what we have learned from recent studies? Susan L.

of Texas San Antonio, Texas Question # 52: Can you delineate the role and rationale for microtubuletargeting agents for treatment of metastatic breast cancer?

Question # 54: Do we understand the underlying causes of peripheral neuropathy associated with microtubule-targeting agents?

5 Question # 51: How might we meet the challenges of classifying and treating patients with triple negative breast cancer based on what we have learned from recent studies? Susan L. Mooberry, PhD Professor of Pharmacology Co leader of Experimental and Developmental Therapeutics Cancer Therapy and Research Center University of Texas Health Science Center at San Antonio University of Texas San Antonio, Texas Question # 52: Can you delineate the role and rationale for microtubuletargeting agents for treatment of metastatic breast cancer? Question # 53: Can you compare the expected side effects of microtubule-targeting agents, based on results reported in recent clinical and animal trials? Question # 54: Do we understand the underlying causes of peripheral neuropathy associated with microtubule-targeting agents? Question # 55: What are the differences in mechanism of action and clinical properties of the various approved microtubuledisrupting agents used in advanced and MBC? Question # 56: Are the microtubule-targeting agents sufficiently differentiated in their mechanisms of action and clinical effects to permit responsiveness to a second microtubule-directed agent after failure of an initial microtubule-targeted drug? Question # 57: In addition to metastatic breast cancer, what types of tumors are likely to be amenable to therapy with microtubule-targeting agents? Question # 58: Can you explain the mechanistic underpinnings of microtubule architecture and why microtubule-targeting agents have shown to be effective in advanced and MBC? Question # 59: What are the anti-mitotic properties of microtubule-targeting agents and how do these disruptions of microtubule dynamics help explain their anti-tumor effects? Question # 60: Can we view microtubule-inhibiting agents as a drug class, or do individual agents, such as eribulin, that disrupt microtubule dynamics need to be considered based on their unique mechanisms, binding sites, and clinical properties? Ricardo Alvarez, MD, MSc Assistant Professor Department of Breast Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Assistant Professor, The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic Houston, Texas Question # 61: Can you review our armamentarium of microtubuletargeting agents for metastatic breast cancer? Question # 62: From your perspective, how should we translate the results of the 301 trial into the front lines of treatment for MBC, especially in patients with highly proliferative tumor types? Question # 63: What were the overall survival results for eribulin versus capecitabine in the pre-specified (triple negative) cohorts of the 301 trial? What are the clinical implications of these findings? Question # 64: In the clinic, how do you stage- or risk-stratify breast cancer patients with metastatic diseased based on receptor status and other markers? How have the trials helped us sort out these issues? Tiffany A. Traina, MD Assistant Professor Weill Medical College of Cornell University Assistant Attending Physician Memorial Sloan Kettering Cancer Center New York, New York Question # 65: What does the sequencing algorithm for microtubule inhibitors currently look like for metastatic breast cancer? Question # 66: From your perspective, what was the rationale and justification for the 301 trial? Question # 67: Can you address the specifics of the eribulin versus capecitabine 301 trial, including the dosages involved, planned subset analysis, end points, and real world issues illuminated and evaluated by the trial? Question # 68: Can you summarize the results of the 301 trial and what you, as a breast cancer specialist, learned and are likely to translate into clinical practice based on the trial s findings? Question # 69: With respect to patient subtypes those with highly proliferative, rapidly progressive tumors in the triple receptor negative cohort what issues and possible strategies for daily practice are brought forward by the 301 trial? Question # 70: As an expert assessing and managing triple negative patients with MBC, can you provide us with your synthetic perspective, based on the 301 trial and other data, on how to optimize management in this challenging population? Question # 71: Based on the latest data available, what is your current sequencing algorithm for MBC? YOUR PATIENTS EXPERT CONSULTATIONS

Question # 72: Can you provide an alignment of specific therapies based on biomarker profiles and receptor status with advanced breast cancer? How do select specific therapies for specific subsets?

How does the 301 trial fit into your analysis? Katherine H.

patients with MBC after they have failed adjuvant chemotherapy with an anthracycline plus a taxane?

6 Question # 72: Can you provide an alignment of specific therapies based on biomarker profiles and receptor status with advanced breast cancer? How do select specific therapies for specific subsets? Question # 73: As an expert on managing breast cancer patients with triple negative status, what do you see as the special challenges, issues, and unmet needs in this patient population? How does the 301 trial fit into your analysis? Katherine H. Rak Tkaczuk, MD and Oncology Director, Breast Evaluation and Treatment Program Medical Oncologist University of Maryland Medical Center Baltimore, Maryland Question # 74: What is your approach to patients with MBC after they have failed adjuvant chemotherapy with an anthracycline plus a taxane? Question # 75: Based on the evidence available thus far, what kind of patient do you consider to be an appropriate, or even ideal, candidate for eribulin therapy? Question # 76: What is your approach to the triple negative patient with advanced breast cancer? Amelia Zelnak, MD, MSc Assistant Professor of Hematology and Oncology Winship Cancer Institute Emory University School of Medicine Atlanta, Georgia Question # 77: What practical approaches to sequencing endocrine or chemotherapy-based agents do you use for survival prolongation in patients with metastatic breast cancer? Question # 78: Within your framework for sequencing agents for survival prolongation in MBC, how do you choose among the individual options that are available? Among the microtubule-targeting agents? Question # 79: How, in your view, has the 301 Trial helped us sort out how we might approach certain subsets of patients with advanced breast cancer, especially triple negative patients? Question # 80: If survival prolongation is the principal objective what approach do you recommend? Virginia Kaklamani, MD Associate Professor Division of Hematology/Oncology Northwestern University Feinberg School of Medicine Chicago, Illinois Question # 81: What is your approach to patients with breast cancer who have received a taxane in the adjuvant setting and who subsequently develop progressive disease? Question # 82: How have the EMBRACE and other trials helped guide your treatment approach and chemotherapy sequencing strategies at the front lines of treatment for MBC? How has this affected your sequencing strategy for eribulin, specifically? Question # 83: What are the clinical implications of previous trials evaluating capecitabine in triple negative MBC and what additional information doe the 301 Trial provide about eribulin versus capecitabine in this patient subset? Question # 84: Where should we be looking for advances in the management of advanced and MBC? Lee S. Schwartzberg, MD FACP Medical Director, The West Clinic Clinical University of Tennessee College of Medicine Memphis, Tennessee Question # 85: How do we use timing and previous exposure to specific lines of adjuvant therapy to select chemotherapeutic agents in refractory breast cancer? Can you give a real world example? Question # 86: How do we sequence and combine agents in early versus late line therapy? Question # 87: Where do we stand as far as personalizing therapy for advanced stage and MBC based on biomarkers, receptors, and proteonomics? Question # 88: When survival prolongation is the principal treatment goal for patients in later line settings, what evidence basis do you use to make your clinical decisions? Question # 89: How does peripheral neuropathy and other toxicities influence your decision to use or select among microtubule-targeting agents? YOUR PATIENTS OPTIMAL INTERVENTIONS

7 Joyce O Shaughnessy, MD Baylor Sammons Cancer Center in Dallas Co Chair, Breast Cancer Research Chair, Cancer Prevention Research U.S. Oncology Clinical Trials Network Houston, Texas Question # 90: What clinical features and biomarker profiles do you rely on to make decisions regarding use of microtubule-targeting agents for treatment of MBC? Question # 91: How do we use mechanisms of action, side effects, and toxicities to govern our deployment and dosing of microtubule-targeted agents for advanced breast cancer? Question # 92: How do mechanisms of action for eribulin and the taxanes help explain differential side effect profiles and non-cross resistance? Question # 93: In the heavily pre-treated subgroup with MBC, how do you use trial-based evidence to drive your clinical treatment algorithm? How do you navigate among all the options? Question # 94: How do you approach patients with triple negative breast cancer? What is the role of eribulin in these challenging patients? Peter A. Kaufman, MD Associate Department of Medical Oncology and Hematology Dartmouth Medical School Norris Cotton Cancer Center Lebanon, New Hampshire Question # 95: Can you summarize the design, rationale, and objectives for the 301 Trial comparing eribulin and capecitabine? Question # 96: What were the results of 301 Trial and can you summarize the results of the exploratory analysis looking at prespecified subgroups based on receptor status? Question # 97: What do the results including survival and side effects of the 301 Trial suggest on a practical level for use of eribulin and capecitabine in specific subsets of patients with MBC following adjuvant therapy? Question # 98: Despite failure to reach target outcomes for the primary end points in the 301 Trial, what should clinicians take away from what is, nevertheless, a wealth of new data comparing two important agents used in MBC? Question # 99: How do mechanisms of action for eribulin and the taxanes help explain differential side effect profiles cross resistance patterns? Question # 100: What are the implications of new trials for personalizing treatment of breast cancer? YOUR CLINICAL CASES EXPERT STRATEGIES

8 Interactive Medical Intelligence Experts Address Critical Questions and Performance Gaps in Clinical Medicine YOUR CLINICAL CASES EXPERT STRATEGIES

9 YOUR QUESTIONS EXPERT DISCUSSION

10 YOUR QUESTIONS EXPERT ANALYSIS

11 YOUR QUESTIONS EXPERT DISCUSSION

Finding the Positives in Triple-Negative Breast Cancer:

Finding the Positives in Triple-Negative Breast Cancer: A Three-Part Live CME Webcast Series Seminar I Wednesday, March 3, 2010 Faculty Clifford Hudis, MD Lisa A Carey, MD Seminar II Thursday, March 11,