OBR Daily Commentary

forumImage

CheckMate -9LA, a Phase 3 Trial Evaluating Opdivo (nivolumab) Plus Low-Dose Yervoy (ipilimumab) Combined with Chemotherapy, Meets Primary Endpoint Demonstrating Superior Overall Survival Compared to Chemotherapy Alone in First-Line Lung Cancer

(BMS) Oct 22, 2019 - Study evaluated Opdivo plus low-dose Yervoy given concomitantly with two cycles of chemotherapy vs. chemotherapy alone for the first-line treatment of advanced non-small cell lung cancer. Bristol-Myers Squibb Company today announced that CheckMate -9LA, a pivotal Phase 3 trial evaluating Opdivo (nivolumab) plus low-dose Yervoy (ipilimumab) given concomitantly with two cycles of chemotherapy for the first-line treatment of advanced non-small cell lung cancer (NSCLC), met its primary endpoint of superior overall survival (OS) at a pre-specified interim analysis. The comparator in this study was chemotherapy alone for up to four cycles followed by optional maintenance therapy. The safety profile of Opdivo plus low-dose Yervoy and two cycles of chemotherapy in CheckMate -9LA was reflective of the known safety profiles of the immunotherapy and chemotherapy components in first-line NSCLC.

Read Article arrow

H. Jack West, MD (Posted: October 24, 2019)

quotesThis will surely be an interesting trial to see the data on, but I suspect it will have little direct impact on treatment of patients with advanced NSCLC. Chemo/immunotherapy combinations based on KEYNOTE-189 (carbo/-pemetrexed/pembro) for non-squamous NSCLC or KEYNOTE-407 (carbo/taxane/pembro) for squamous NSCLC are already a strong standard of care, and either pembro monotherapy for selected patients (most appropriate for those with high tumor PD-L1 expression, based on KEYNOTE-024 trial) or now possibly nivo/ipi for others based on CheckMate-227 are available for those in whom a chemo-free option is preferred. This 4 drug regimen beat an older standard of care that has already been improved upon with all of the regimens listed above, and we should expect it to have a more unfavorable side effect profile than any of these alternatives. Unless the data suggest it is strikingly superior to these other options, I think it will prove to have nothing to recommend it over an option that we already have (or are likely to have once nivo/ipi is approved based on the benefit observed in CM-227).quotes

Add Comment 1 Comment
forumImage

Lilly's CYRAMZA® (ramucirumab) Phase 3 Data in First-Line EGFR-Mutated Non-Small Cell Lung Cancer Published in The Lancet Oncology

(Lilly) Oct 7, 2019 - CYRAMZA, in combination with erlotinib, significantly delayed disease progression in previously untreated patients with metastatic non-small cell lung cancer whose tumors have activating EGFR mutations. In the RELAY study, treatment with CYRAMZA in combination with erlotinib demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) – the time patients lived without their cancer growing or spreading after starting treatment – compared to erlotinib alone.

Read Article arrow

H. Jack West, MD (Posted: October 07, 2019)

quotesThough the progression-free survival (PFS) for this global trial is very encouraging, we've seen other work out of Japan on erlotinib + VEGF inhibitor (bevacizumab previously) demonstrate a highly significant improvement in PFS that didn't translate into an improvement in overall survival (OS). I would say that based on the Japanese research, plus with the added burden of regular IV infusions added to an otherwise oral regimen, and the lack of CNS activity compared to the competing standard of osimertinib, I don't think this combination regimen will gain much traction in the absence of further follow-up demonstrating a significant OS benefit.quotes

Add Comment 1 Comment
forumImage

Two Immunotherapy Drug Combination Offers Chemotherapy-Free Option for Advanced NSCLC

(ESMO 2019) Sept 28, 2019 - New data have shown that first-line treatment with a combination of two immunotherapy drugs improves overall survival in a subset of patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy (1). The data from the CheckMate-227 trial, reported at the ESMO Congress 2019, suggest that the combination of nivolumab plus low-dose ipilimumab could offer a chemotherapy-free option for first-line treatment of patients with advanced NSCLC. Nivolumab, a PD-1 antibody, and ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, are immune checkpoint inhibitors with distinct but complementary mechanisms of action.

Read Article arrow

H. Jack West, MD (Posted: October 01, 2019)

quotesThe impact of the CheckMate-227 trial remains to be seen. While it was positive for an overall survival benefit, this was observed in the patients with PD-L1 expression 50%, but not in the patients with PD-L1 expression in between. This pattern doesn't give us a lot of confidence. At the same time, the OS benefit was compared to chemo alone, while the current standard of care is now chemo/pembro in most of these patients (certainly those with PD-L1 <1%), in whom there was a significant survival benefit seen in the KEYNOTE-189 and KEYNOTE-407 trials for patients with advanced non-squamous and squamous NSCLC, respectively. I expect that the appeal of a non-chemotherapy regimen will have some appeal to patients and oncologists, but we should recognize that non-chemo doesn't mean non-toxic. I expect that nivo/ipi will be a minor player compared to our current standards, likely used in <10% of patients in front line advanced NSCLC.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

Associate Clinical Professor, Medical Oncology Executi...

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...