“Although checkpoint blockade immunotherapies have advanced rapidly in the treatment paradigm for patients with non–small cell lung cancer (NSCLC), interest in developing targeted therapies for this malignancy has remained high. Building on the success of molecularly targeted drugs aimed at relatively small subsets of patients, researchers are increasingly aiming at the MET oncogene.
“During the past several years, interest in MET activity has grown as investigators have considered it both as a biomarker and target for treatment, particularly since the focus on MET exon 14 skipping mutations has led to the development of several second-generation MET inhibitors, according to Balazs Halmos, MD, MS.”
“The primary endpoint of improving overall survival (OS) was not met in the phase III JAVELIN Lung 200 Trial of avelumab (Bavencio) in patients with non–small cell lung cancer (NSCLC), according to Merck KGaA and Pfizer, the co-developers of avelumab.
“According to results of the study, the PD-L1 inhibitor did not improve OS for patients with PD-L1-positive (≥1%) unresectable, recurrent or metastatic NSCLC compared with docetaxel in patients who had progressed on platinum-containing doublet chemotherapy (hazard ratio [HR], 0.90; 96% CI, 0.72-1.12; one-sided P = .1627).”
“Recently reported updates from the KEYNOTE-189 and IMpower150 trials demonstrated the powerful impact of adding immunotherapy to treatment regimens for patients with non–small cell lung cancer (NSCLC).
“In the phase III KEYNOTE-189 study, the combination of pembrolizumab (Keytruda) with chemotherapy in the frontline setting improved survival in patients with nonsquamous NSCLC. In this trial, which is the confirmatory trial for the FDA approval of pembrolizumab plus carboplatin/pemetrexed, patients received frontline pembrolizumab or placebo combined with pemetrexed and either cisplatin or carboplatin. The study met the primary endpoints of improved overall survival (OS) and progression-free survival (PFS), though full data have yet to be presented.”
“The U.S. Food and Drug Administration today approved Imfinzi (durvalumab) for the treatment of patients with stage III non-small cell lung cancer (NSCLC) whose tumors are not able to be surgically removed (unresectable) and whose cancer has not progressed after treatment with chemotherapy and radiation (chemoradiation).”
“On February 12, the U.S. Food and Drug Administration (FDA) accepted and granted Priority Review to Pfizer’s new drug application for lorlatinib. The Prescription Drug User Fee Act goal date for a decision by the FDA is in August 2018.
“Lorlatinib is an investigational, anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor for the treatment of patients with ALK-positive metastatic non–small cell lung cancer (NSCLC) previously treated with one or more ALK tyrosine kinase inhibitors. It has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of both ALK and ROS1. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood-brain barrier.”
“The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) improved progression-free survival (PFS) compared with chemotherapy in treatment-naïve patients with high tumor mutation burden (TMB) non–small cell lung cancer (NSCLC).
“Bristol-Myers Squibb (BMS), the manufacturer of both immunotherapies, announced the preliminary findings from part 1a of the phase III CheckMate-227 trial in a press release. The company did not report any further data.”
“The frontline indication for afatinib (Gilotrif) has been expanded by the FDA to include the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors harbor uncommon EGFR alterations in L861Q, G719X, and/or S768I.
“The FDA initially approved afatinib in 2013 for the treatment of patients with metastatic NSCLC with exon 19 deletions or exon 21 L858R substitutions. In 2016, the FDA expanded the indication to include patients with squamous histology following progression on a platinum-based chemotherapy.”
“The addition of pembrolizumab to pemetrexed and cisplatin or carboplatin improved OS and PFS as first-line treatment for patients with metastatic nonsquamous non-small cell lung cancer, according to a manufacturer-issued press release.
Diagnosis of adenocarcinoma of the lung, a major subtype of non-small lung cancer (NSCLC), nowadays triggers mandatory testing of tumor tissue for alterations in four genes: EGFR, ALK, ROS1, and more recently, BRAF. If present, these alterations predict sensitivity to specific targeted drugs approved by the U.S. Food and Drug Administration (FDA) that work better and often longer than standard chemotherapy, and are better tolerated.
However, there are many more targetable/actionable genomic alterations (also known as “drivers”) in NSCLC. This blog post will briefly discuss most of them, with the goal of promoting molecular testing for more than the four “usual suspects” mentioned above. Some patients with these alterations may benefit from FDA-approved drugs or from enrollment in clinical trials that are testing additional drugs and drug combinations. Continue reading…