OBR Daily Commentary

forumImage

MEK Inhibitor Disappoints in KRAS-Mutant NSCLC

(MedPage Today) May 9, 2017 - A targeted combination therapy for patients with KRAS-mutant non-small cell lung cancer (NSCLC) did not improve overall survival (OS) or progression-free survival (PFS), researchers reported.

Read Article arrow

H. Jack West, MD (Posted: May 10, 2017)

quotesThe clearest point of this manuscript was that this trial showed no hint of the provocative benefit seen with the combination of docetaxel and the MEK inhibitor selumetinib in a prior phase II trial. We can debate potential explanations, and the authors and editorialists offer several hand-waving possibilities, but the only thing we definitely know is that this is yet one more stark example of a very promising phase II trial followed by a stone cold negative phase III trial, as we've seen with figitumumab, onartuzumab, ASA-404, talactoferrin, and a long list of other agents/trials. I don't know how many times we'll need to see this pattern before we control our hubris in calling a definitive win based on encouraging phase II data. With modest numbers of patients from a very limited number of treating centers, phase II trials are clearly a poor substitute for the broader clinical experience drawn from phase III randomized trials.quotes

Add Comment 1 Comment
forumImage

ELCC 2017 Press Release: Patients With Non-Small-Cell Lung Cancer Respond Best to Salvage Chemotherapy When Pre-Treated With PD-1/PD-L1 Inhibitors

(ESMO) May 4, 2017 - Patients with advanced non-small-cell lung cancer (NSCLC) who require salvage chemotherapy are 30% more likely to achieve a partial response if they have been pre-treated with a PD-1/PD-L1 checkpoint inhibitor compared to those who have not, according to a study to be presented at the European Lung Cancer Conference (ELCC) 2017 in Geneva, Switzerland.

Read Article arrow

H. Jack West, MD (Posted: May 04, 2017)

quotesThese results are very provocative, but we need a larger, randomized study to say anything more definitive about whether great activity of chemotherapy after rather than preceding immunotherapy is a reason to change how we typically sequence systemic lung cancer therapies. We will see far more studies of immunotherapy in the first line setting over the next few years, and it will be helpful to assess whether this finding is commonly demonstrated.quotes

Add Comment 1 Comment
forumImage

FDA Approves Alunbrig (brigatinib) for Rare Lung Cancer

(Rare Disease Report) Apr 29, 2017 - On Friday evening, Takeda Pharmaceuticals announced the FDA has approved Alunbrig (brigatinib) to treat patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

Read Article arrow

H. Jack West, MD (Posted: May 01, 2017)

quotesThe data with brigatinib are strong, as this is an agent that has impressive activity against a broad range of secondary mutations in ALK preclinically, and clinically it is the first second generation ALK inhibitor that demonstrates a median progression-free survival beyond one year. Although the various second generation ALK inhibitors have yet to be compared directly to each other, the results with brigatinib are favorable in cross-trial comparisons. It is also typically well tolerated, though the potential for early pulmonary toxicity in the first few days requires attention and some caution (this is the reason for the escalation from 90 to 180 mg daily after one week). But the landscape of ALK-positive advanced NSCLC is about to be transformed with the presentation of the results of the global ALEX trial, expected to be at ASCO. This phase III study of alectinib vs. crizotinib in ALK inhibitor-naive patients was recently noted to be positive for a PFS benefit with alectinib, and if it is even half of the demonstrated PFS benefit demonstrated in the smaller and Japanese-only J-ALEX trial reported at ASCO 2016 (Nokihara, A#9008), it should be enough to change practice and make alectinib the first line therapy of choice for ALK-positive NSCLC. That will leave brigatinib likely relegated to post-alectinib, where it may have far less activity than after crizotinib, since brigatinib and alectinib are both second generation ALK inhibitors and may have significant cross-resistance between them. It's certainly great to have another effective ALK inhibitor available for patients, and we'll need further data to see how brigatinib looks in first line (trial ongoing, vs. crizotinib) as well as its activity after alectinib. We'll also need to keep an eye out for lorlatinib, a third generation ALK inhibitor with activity even after acquired resistance to second generation ALK inhibitor therapy, and other ALK inhibitors in development.quotes

Add Comment 1 Comment

Meet the Editorial Board

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

Associate Cancer Center Director, Yale Cancer Center P...

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...