OBR Daily Commentary - Lung (includes NSCLC, SCLC, Mesothelioma)

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In Another Lung Cancer Setback, Bristol Yanks FDA App For Drug Combo

(Xconomy New York) Jan 24, 2019 - Bristol-Myers Squibb has lost yet more ground in its ongoing cancer immunotherapy battle with rival Merck. Along with its earnings, the pharma firm reported Thursday that it has pulled a key approval application to use a combo regimen of its already approved immunotherapies, nivolumab (Opdivo) and ipilimumab (Yervoy), in a portion of patients with newly diagnosed, advanced non-small cell lung cancer (NSCLC). Specifically, Bristol said that, upon discussions with the FDA, it needs more data to support the approval filing. The problem: Bristol needs to provide additional evidence for “the relationship between [tumor mutational burden] and PD-L1”—two biomarkers meant to help identify patients who might respond to immunotherapy—to really tell if the Bristol regimen is helping patients live longer.

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

quotesWe are not privy to the data that the FDA have, but based on the TMB data that are publicly available, I think this is a very appropriate guidance by the FDA. We need more and stronger data to support TMB use for clinical decision-making. First, we need to see a survival benefit by using it; second, we need to see that the survival benefit is predicated on using the TMB test. I think it is more likely than not that TMB will be a useful biomarker, but not the only one, in a few years. However, the data we've seen from CheckMate-227 are not sufficient to warrant using it.quotes

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FDA Accepts Roche’s Supplemental Biologics License Application For Tecentriq Plus Chemotherapy (Abraxane And Carboplatin) For The Initial Treatment Of Metastatic Non-squamous Non-small Cell Lung Cancer

(Roche) Jan 17, 2019 - Roche today announced that the US Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) for Tecentriq® (atezolizumab) in combination with Abraxane® [albumin-bound paclitaxel; nab-paclitaxel]) and carboplatin for the initial (first-line) treatment of people with metastatic non-squamous non-small cell lung cancer (NSCLC) who do not have EGFR or ALK genomic tumour aberrations. The FDA is expected to make a decision on approval by 2 September 2019. “We look forward to working with the FDA in order to bring this Tecentriq-based combination to people with non-squamous non-small cell lung cancer as soon as possible,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Lung cancer is a challenging disease to treat, and this review takes us one step closer towards offering a new treatment option that has shown a clinically meaningful survival benefit in the treatment of this type of disease.”

H. Jack West, MD (Posted: January 17, 2019)

quotesThis application is based on the results of the IMpower130 trial of first line carbo/nab-paclitaxel with or without atezolizumab in patients with advanced non-squamous NSCLC (disclosure: I am an author on the abstract presented thus far and future publication). The trial is positive for not just an improvement in progression-free survival but also overall survival, which is an achievement. However, I see the limiting factor being that the true comparator in this setting today isn't chemotherapy alone, as was in the trial, but the KEYNOTE-189 combination of carbo/pemetrexed/pembrolizumab in the same setting. Though there can always be an occasion for which an alternative to the carbo/pemetrexed backbone is needed, this chemo regimen and the KEYNOTE-189 combination in general is one that the vast majority of lung cancer specialists and general oncologists alike are very happy to use as their preferred regimen. This will likely relegate the IMpower130 combination being considered here to very, very limited use. There is simply little to no incremental benefit it offers over KEYNOTE-189 in the same setting.quotes

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Merck Provides Update on KEYTRUDA® (pembrolizumab) Supplemental Biologics License Application (sBLA) for KEYNOTE-042 Trial

(Merck) Dec 20, 2018 - Merck today announced that the U.S. Food and Drug Administration (FDA) has extended the action date for the supplemental Biologics License Application (sBLA) for KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express PD-L1 (tumor proportion score [TPS] ≥1%) without EGFR or ALK genomic tumor aberrations. The sBLA is based on results of the Phase 3 KEYNOTE-042 trial where KEYTRUDA monotherapy demonstrated a significant improvement in overall survival compared with chemotherapy in this patient population. The company recently submitted additional data and analyses to the FDA, which constitutes a major amendment and extends the Prescription Drug User Fee Act (PDUFA), or target action date, by three months to April 11, 2019. Merck continues to work closely with the FDA during the review of this sBLA.

H. Jack West, MD (Posted: December 21, 2018)

quotesThis is an indication that, if approved, most lung cancer specialists won't be eager to support. Though patients with PD-L1 1-49% were included in the KEYNOTE-042 trial that came out positive, the subsets clearly illustrate that the study was positive DESPITE their inclusion, which just diluted the real benefit with pembro in the PD-L1>50% population already known to benefit from pembro over chemo based on the KEYNOTE-024 trial. And while you could argue that pembro coming out with the same survival as first line chemo in the PD-L1 1-49% group represents a favorable option since patients can do just as well without the side effects of chemo, this isn't really true. The control arm getting first line chemo wasn't permitted to cross over, and only 20% of these patients ever got access to immunotherapy upon progression, which is a clear standard of care that has a consistently proven survival benefit. In other words, first line pembro merely looks comparable to first line chemo in survival for patients with PD-L1 1-49% who received substandard care on the control arm. First line pembro is a poor option for patients with PD-L1 1-49% who are candidates for chemo/immunotherapy, or arguably even chemo followed by immunotherapy. KEYNOTE-042 should not be interpreted as making first line pembro a compelling option for these patients.quotes

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Meet the Editorial Board

Prostate Cancer
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Tomasz M. Beer, MD, FACP

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

Community Oncology
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Dean Gesme, MD

FACP FACPE FASCO President, Minnesota Oncology...

Breast Cancer
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Debu Tripathy, MD

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

Lung Cancer
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H. Jack West, MD

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

Gastrointestinal Cancers
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Howard S. Hochster, MD

Distinguished Professor of Medicine, Rutgers Robert Woo...

Radiation Oncology
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Howard Sandler, MD, MS, FASTRO

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

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Jeff Patton, M.D.

CEO Tennessee Oncology...

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Jennifer Levin Carter, MD, MPH

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

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Michael G. King Jr.

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Richard Goldberg, MD

Director WVU Cancer Institute Director of Cancer Signa...

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Robert A. Figlin, MD., FACP

Professor and Director, Division of Hematology Oncology...

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Ted Okon

Executive Director Community Oncology Alliance...

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Thomas Marsland, MD

Vice President Integrated Community Oncology Network ...

Community Oncology
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William Harwin MD

Florida Cancer Specialists President and Managing Part...

Health Policy
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William McGivney, PhD

National Health Policy Expert...

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Winston Wong, PharmD

President, W-Squared Group...