OBR Daily Commentary

forumImage

Trastuzumab Deruxtecan Demonstrated Clinically-Meaningful Response In Patients With Refractory HER2-positive Metastatic Breast Cancer, A Population With High Unmet Need

(AstraZeneca) May 8, 2019 - AstraZeneca and Daiichi Sankyo Company, Limited today announced positive top-line results for the pivotal Phase II DESTINY-Breast01 trial of trastuzumab deruxtecan (DS-8201). The HER2-targeting antibody drug conjugate (ADC) and potential new medicine was evaluated in patients with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine.

Read Article arrow

Debu Tripathy, MD (Posted: May 08, 2019)

quotesThe development of testing of new antibody-drug conjugates (ADCs, also known as immunoconjugates) is rapidly growing as these agents allow for more cancer cell-specific drug delivery and the use of more potent cytotoxic drugs than can be given by conventional administration. Every such drug has its own "operating characteristics" depending on the antibody/antigen system used, the nature of the linker attaching the antibody to the active drug and the cytotoxic "payload". In the case of trastuzumab deruxtecan, impressive response rates were shown in pretreated patients with HER2+ breast cancer the Phase I setting. Responses nearing 50% were even shown in a separate cohort of patients who had lower HER2 expression in the negative range by conventional definitions. While the results of the Phase II trial have not yet been made public, there is significant enthusiasm as the Phase III registration trials for both HER2+ and HER2-low get off the ground.quotes

Add Comment 2 Comment
forumImage

FDA Approves Ado-Trastuzumab Emtansine For Early Breast Cancer

(FDA.gov) May 3, 2019 - On May 3, 2019, the Food and Drug Administration approved ado-trastuzumab emtansine (KADCYLA, Genentech, Inc.) for the adjuvant treatment of patients with HER2-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Patients should be selected based on an FDA-approved companion diagnostic for ado-trastuzumab emtansine. FDA also approved both the Ventana Medical Systems, Inc. PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay and the INFORM HER2 Dual ISH DNA Probe Cocktail assay as companion diagnostic devices for selecting patients.

Read Article arrow

Debu Tripathy, MD (Posted: May 07, 2019)

quotesThe approval of T-DM1 (ado trastuzumab emtansine) in the adjuvant setting for patients who have residual disease after standard neoadjuvant (pre-operative) therapy for HER2+ breast cancer is a breakthrough for two very important reasons. First, it has a large effect - cutting recurrence risk by 50% in a high-risk group of patients. That alone is a notable achievement. However, in a larger sense, it establishes that pre-operative therapy is not only a treatment that might help shrink breast cancers in order to allow for less aggressive surgery (eg. breast-conserving surgery), but that it is actually a "bioassay" that helps determine which treatment after surgery is most effective. While we have long been using pre-operative therapy as a way to potentially personalize treatment, this is the first actual demonstration that we can put this theory into practice. We are going to see further advances in "precision" medicine by real-time monitoring during treatment to determine what the best next step is for each unique case, and to accelerate the testing of new therapies using this platform. So while the practical result for now is the approval of an established drug in the advanced setting for a new indication in early stage setting - it has much broader implications going forward.quotes

Add Comment 1 Comment
forumImage

U.S. FDA Approves IBRANCE® (palbociclib) for the Treatment of Men with HR+, HER2- Metastatic Breast Cancer

(Pfizer) Apr 4, 2019 - Approval of expanded indication based predominately on real-world data. Pfizer today announced that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to expand the indications for IBRANCEĀ® (palbociclib) in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. The approval is based on data from electronic health records and postmarketing reports of the real-world use of IBRANCE in male patients sourced from three databases: IQVIA Insurance database, Flatiron Health Breast Cancer database and the Pfizer global safety database.

Read Article arrow

Debu Tripathy, MD (Posted: April 06, 2019)

quotesThis label approval of palbociclib for male breast cancer is an example of creativity to address subsets of patients rarely represented in clinical trials, yet for whom it is plausible that the results may not reflect the main study findings. This subsets typically include males (in the field of breast cancer) as well as older patients, pediatric patients or those with varying degrees of organ dysfunction. Small trials used to be required to extend the label to these subsets (although often physicians would just their own judgment, but then may get challenged by insurance companies. This approval is interesting in that it is based on part on new sources of "real-world" data, large data aggregators like Flatiron Health, where outcomes are analyzed based on "big data", including electronic medical records in some cases. We may see more of this - in fact, it is possible that clinical research for some of the less complex diseases will migrate to being primarily conducted in this environment.quotes

Add Comment 1 Comment

Meet the Editorial Board

Prostate Cancer
member photo
Tomasz M. Beer, MD, FACP

Professor of Medicine, Division of Hematology/Medical O...

Community Oncology
member photo
Dean Gesme, MD

FACP FACPE FASCO President, Minnesota Oncology...

Breast Cancer
member photo
Debu Tripathy, MD

Professor and Chair, Department of Breast Medical Oncol...

Lung Cancer
member photo
H. Jack West, MD

Medical Director, Thoracic Oncology Program, Swedish Ca...

Gastrointestinal Cancers
member photo
Howard S. Hochster, MD

Distinguished Professor of Medicine, Rutgers Robert Woo...

Radiation Oncology
member photo
Howard Sandler, MD, MS, FASTRO

Ronald H. Bloom Chair in Cancer Therapeutics
Pr...

Community Oncology
member photo
Jeff Patton, M.D.

CEO Tennessee Oncology...

Precision Medicine Section Editor
member photo
Jennifer Levin Carter, MD, MPH

Chief Medical Officer and Founder, N-of-One...

Financial Sector
member photo
Michael G. King Jr.

Managing Director and Senior Biotechnology Analyst...

Gastrointestinal Cancers
member photo
Richard Goldberg, MD

Director WVU Cancer Institute Director of Cancer Signa...

Editor-In-Chief
member photo
Robert A. Figlin, MD., FACP

Professor and Director, Division of Hematology Oncology...

Health Policy
member photo
Ted Okon

Executive Director Community Oncology Alliance...

Community Oncology
member photo
Thomas Marsland, MD

Vice President Integrated Community Oncology Network ...

Community Oncology
member photo
William Harwin MD

Florida Cancer Specialists President and Managing Part...

Health Policy
member photo
William McGivney, PhD

National Health Policy Expert...

Payer
member photo
Winston Wong, PharmD

President, W-Squared Group...