OBR Daily Commentary

forumImage

Bristol-Myers Squibb Announces CheckMate -451 Study Did Not Meet Primary Endpoint of Overall Survival with Opdivo Plus Yervoy Vs. Placebo as A Maintenance Therapy in Patients with Extensive-Stage Small Cell Lung Cancer After Completion of First-Line Chemotherapy

(BMS) Nov 26, 2018 - Bristol-Myers Squibb Company today announced that the Phase 3 CheckMate -451 study did not meet its primary endpoint of overall survival (OS) with Opdivo (nivolumab) 1 mg/kg in combination with Yervoy (ipilimumab) 3 mg/kg versus placebo as a maintenance therapy for patients with extensive-stage small cell lung cancer (SCLC) without disease progression after completion of first-line platinum-based chemotherapy. No new safety signals were observed with Opdivo 1 mg/kg plus Yervoy 3 mg/kg in this study. The Company will work with study investigators on the future publication of these results. CheckMate -451 is a global, double-blind, randomized Phase 3 study evaluating Opdivo in combination with Yervoy and Opdivo monotherapy versus placebo as a maintenance therapy in patients with extensive-stage small cell lung cancer without disease progression after completion of first-line platinum-based chemotherapy. The primary endpoint of the study is overall survival (OS) with Opdivo plus Yervoy versus placebo. The secondary endpoint is OS with Opdivo monotherapy versus placebo.

Read Article arrow

H. Jack West, MD (Posted: November 27, 2018)

quotes

This is a big miss. Though even a positive result would need to be weighed for significance relative to the positive results for chemo/atezolizumab in the first line IMpower133 trial, the fact that this trial failed to improve survival compared to placebo in the maintenance setting is a great disappointment, especially on top of the recently reported (though only as a press release thus far) negative result on the CheckMate-331 trial of nivolumab alone vs. 2nd line chemo for relapsed SCLC. This result leads me to be far less inclined to consider either nivo or nivo/ipi as a very compelling option in relapsed SCLC, despite the FDA approval of nivo in this setting (actually 3rd line) earlier this year, or based on the Checkmate-032 phase II trial, which seems in retrospect to be yet another reminder of the power of selection bias. Should the emerging results also cloud our view on the utility of nivolumab +/- ipilimumab in NSCLC? Not enough to counter strong data, but we don't have particularly strong data in first line NSCLC at this time.

These negative results on CheckMate-451 also do not challenge the current concept of integrating immunotherapy into first line treatment for SCLC rather than deferring it as maintenance or 2nd line treatment. Though some are disappointed by the only relatively modestly positive results of IMpower133 with carbo/etoposide +/- atezolizumab, the significant improvement in OS should be sufficient to consider this approach the current standard of care for eligible patients. And the recent results with nivo +/- ipi in SCLC only underscore that significant gains in survival for patients with SCLC are quite hard to come by.

quotes

Reply

Add Comment 1 Comment(s)

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...