The 3rd Stat4Onc Annual Symposium
End-points utilized in cancer clinical trials
Speaker Biography and Abstract
Andrew D. Seidman, MD
Andrew Seidman is an Attending Physician for the Breast Medicine Service at Memorial
Sloan Kettering Cancer Center in New York City, and Professor of Medicine at
Weill Cornell Medical College. He also serves as the Medical Director of
MSKCC’s Bobst International Center. Dr. Seidman earned his medical degree from
Hahnemann University School of Medicine in Philadelphia, Pennsylvania in 1985.
He completed a residency in Internal Medicine at the Pennsylvania Hospital. Dr.
Seidman then completed a fellowship in Medical Oncology and Hematology at
Memorial Sloan Kettering Cancer Center in New York.
Seidman’s clinical research in the development of taxanes
for breast cancer has impacted clinical care worldwide. He has authored or
co-authored more than 200 peer-reviewed articles, reviews and book chapters, as
well as over 150 abstracts, has served on the editorial boards of over a dozen
leading oncology journals, and has lectured at innumerable national and
international conferences and symposia on breast cancer related topics. Dr.
Seidman is a Past-President of the American Society of Breast Disease, the
recipient of a Career Development Award from the American Society of Clinical
Oncology (ASCO) for his work developing taxanes for
breast cancer, the Gay Clark Stoddard Award from the Susan G. Komen Foundation
for excellent and compassionate care of patients with breast cancer, and the
Jacob Ehrenzeller Award from Pennsylvania Hospital
for Academic Excellence and a Distinguished Alumni Award from the Hahnemann
School of Medicine. He recently chaired a Working Group for the National Cancer
Institute’s Breast Cancer Steering Committee on Meaningful and Appropriate
Endpoints for Clinical Trials in Metastatic Breast Cancer (J Clin Oncol 2018). He has served on the ASCO Communications
Committee, as Associate Chair of Academic Administration at MSKCC and as Senior
Breast Cancer Advisor to the MSKCC-IBM Watson Collaboration, developing a
decision-support tool for oncologists. Dr. Seidman has served on the Oncology
Drug Advisory Committee to the U.S. Food and Drug Administration. He currently
leads an active translational research program focused on novel systemic
treatment strategies for breast cancer brain metastases.
and appropriate endpoints for clinical trials in metastatic breast cancer: A
report from the NCI Breast Cancer Steering Committee Working Group
is significant heterogeneity in the natural history of metastatic breast cancer
(MBC), particularly with respect to overall prognosis, treatment options and
benefits of therapy in biologic subtypes. Outcomes in clinical trials depend
upon many variables, including extent and nature of prior therapy, sites and
burden of existing disease, and toxicity. The expected post-progression
survival after completion of protocol-specific therapy has implications for the
choice of optimal endpoint - when overall survival (OS) is measured in years,
and patients receive multiple lines of therapy, progression-free survival (PFS)
may be the most meaningful metric of treatment outcome. Conversely, in poor prognosis settings such as
triple negative metastatic breast cancer (TNMBC), where expected
post-progression survival (PPS) is short, OS is likely the most appropriate
endpoint1. From a patient perspective, the balance between
incremental gain in PFS and encountered toxicity is crucial, though there is
scant data on this topic2. In this context, several recent
randomized trials have yielded statistically significant improvements in the
primary endpoint with experimental therapy, but did not lead to regulatory
approval or practice change3, primarily due to unacceptable toxicity
in the experimental arm. This highlights
the need for guidance on both appropriate endpoints for clinical trials in the
setting of metastatic breast cancer, and for incorporation of patient reported
outcomes (PROs) and toxicities into the discussion of clinical trial design,
conduct and interpretation.
guidance for industry on clinical trial endpoints was provided by the U.S. Food
and Drug Administration (FDA) in 20074, but was not
disease-specific. Patient-focused drug development is mandated by the
Prescription Drug User Fee Act V, and integration of patient reported outcomes
(PROs) in the assessment of benefit of new treatments is evolving. Our Working
Group (WG) sought to create specific consensus on endpoints for MBC clinical
trials focusing on biologic subtype and line of therapy, with sensitivity to
various stakeholders. This presentation will overview some key insights from
Ellis LM, Bernstein DS, Voest EE, et al. American
Society of Clinical Oncology Perspective: Raising the bar for clinical trials
by defining clinically meaningful outcomes. J Clin
Oncol 32(12): 1277-80, 2014.
2. Hurvitz SA, Lalla D, Crosby RD,
Mathias SD. Use of the metastatic breast cancer progression (MBC-P)
questionnaire to assess the value of progression-free survival for women with
metastatic breast cancer. Breast Can Res Treat 142:603-9, 2013.
3. Dickler MN, Barry WT, Cirrincione
CT, et al. Phase III trial evaluating letrozole as first-line endocrine therapy
with or without bevacizumab for the treatment of postmenopausal women with
hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance).
J Clin Oncol 34(22):2602-9, 2016.
Guidance for Industry: Clinical trial endpoints for the approval of cancer
drugs and biologics. (FDA:
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics
Guidance for Industry) .
Seidman AD, Bordeleau L, Fehrenbacher
L, et al. National Cancer Institute Breast Cancer Steering Committee Working
Group Report on Meaningful and Appropriate End Points for Clinical Trials in
Metastatic Breast Cancer. J Clin Oncol. 2018 Sep 13:JCO1800242. doi:
Meredith M. Regan, Sc.D.
M. Regan, Sc.D., is Associate Professor, Division of Biostatistics, Dana-Farber
Cancer Institute (DFCI) and Associate Professor of Medicine, Harvard Medical
School. She earned her doctorate in biostatistics at the Harvard School of
Regan’s research focuses on clinical and translational research to inform
patient care and treatment selection for breast and genitourinary cancers.
is Director of the Statistical and Data Management Center for the International
Breast Cancer Study Group (IBCSG), an international cooperative clinical trials
and clinical-translational research group. She is a past member of the US NCI
Breast Cancer Steering Committee and its working group in endpoints for
clinical trials in metastatic breast cancer. Dr. Regan is also Data
Coordinating Center Director and co-investigator of the Intermediate Clinical
Endpoints in Cancer of the Prostate (ICECaP) Working
Group which aims to validate surrogate endpoints for overall survival that
could expedite the evaluation of new adjuvant therapies for high-risk localized
Tailoring Endpoints in
Later-phase Oncology Clinical Trials
In later-phase oncology clinical trials, overall survival is
classically considered to be the gold-standard endpoint, as we aim to cure or
lengthen the survival of cancer patients. Recent years have brought new focus
on demonstrating classical efficacy endpoints as valid surrogates for overall
survival and on proposing new efficacy endpoints in specific settings. As well,
the statistical measures we estimate are discussed with greater emphasis of
their clinical interpretation and the clinically-meaningful treatment effect.
Toxicity and adverse event endpoints are receiving renewed attention, and
integration of efficacy and toxicity endpoints are being considered. We’ll
discuss tailoring endpoints to the clinical setting, built upon the foundations
of our classical endpoints.
Chakravartty is presently the Global Program
Biostatistics Head of the Breast Cancer Franchise in Novartis. He has been with
Novartis since 2012 and has led the development of multiple cancer indications
and health authority submissions during this period. Most recently Dr. Chakravartty has been leading the submissions of CDK4/6
inhibitors in advanced breast cancer.
Prior to joining Novartis, Dr. Chakravartty
worked as a statistician at Eli Lilly and Abbvie
supporting diabetes and immunology clinical development besides Oncology.
Besides his role in industry Dr. Chakravartty has been
an active contributor and also a peer-reviewer for
multiple biostatistical journals. Most recently he co-authored a book chapter
on Adaptive designs for Statistical Approaches in Oncology Clinical Development
published by CRC press in 2018