“The combination of bevacizumab (Avastin) and erlotinib (Tarceva) is superior to erlotinib alone as upfront treatment for non–small cell lung cancer (NSCLC) harboring EGFR mutations. A preplanned interim analysis of the phase III study known as NEJ026 showed a median progression-free survival (PFS) by independent review (the primary endpoint) of 16.9 months with the bevacizumab/erlotinib combination compared with 13.3 months with erlotinib by itself, said Naoki Furuya, MD, PhD, at the 2018 ASCO Annual Meeting.”
“U.S. regulators have expanded use of AstraZeneca’s lung cancer drug Tagrisso to include initial treatment of patients with a specific genetic mutation, the company said on Wednesday.
“The latest Food and Drug Administration approval includes patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test.
“Tagrisso, also known as osimertinib, was already approved for use in patients whose lung cancer worsened after treatment with other EGFR therapies and who have developed a secondary mutation.”
“Immune checkpoint inhibitors have revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC). In patients progressing on first-line therapy, immunotherapy with the PD-1/PD-L1 inhibitors pembrolizumab, nivolumab, and atezolizumab has become standard second-line therapy. While these agents are associated with durable responses and long-term improvements in overall survival (OS), only a small proportion of patients respond to treatment. Relatively little is known about the factors that predispose patients to response on checkpoint inhibitors, and there is an unmet need for improved patient selection criteria.”
“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.”
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…
“The FDA has granted a priority review to a supplemental new drug application (sNDA) for the use of osimertinib (Tagrisso) as a first-line treatment for patients with non–small cell lung cancer (NSCLC) whose tumors harbor EGFR mutations (exon 19 deletions or exon 21 [L858R] substitution mutations).
“The sNDA is based on the phase III FLAURA study, in which frontline osimertinib reduced the risk of progression or death by 54% versus standard TKI therapy—erlotinib (Tarceva) or gefitinib (Iressa). In the double-blind study, the median progression-free survival (PFS) was 10.2 months (95% CI, 9.6-11.1) for standard therapy and 18.9 months (95% CI, 12.5-21.4) with osimertinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001).”
“Osimertinib (Tagrisso) has impressed researchers in the field of EGFR-mutant non–small cell lung cancer (NSCLC), most recently with results from the phase III FLAURA trial solidifying its benefit.
“In FLAURA, treatment with frontline osimertinib led to a median progression-free survival (PFS) of 18.9 months (95% CI, 15.2-21.4). This represented a 54% risk reduction in progression or death compared with a standard EGFR tyrosine kinase inhibitor (TKI) for patients with locally advanced or metastatic EGFR-mutant NSCLC.”
“The FDA has granted a priority review to a supplemental new drug application (sNDA) for afatinib (Gilotrif) for the frontline treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors harbor EGFR exon 21 (L861Q), G719X, or S768I substitution mutations.
“Uncommon mutations such as these represent less than 10% of the EGFR mutations found in NSCLC patients, but are associated with poor prognosis and survival, Boehringer Ingelheim, the manufacturer of afatinib, noted in a press release.”
“Osimertinib improves progression-free survival by 54% compared to standard first line therapy in patients with EGFR mutated non-small-cell lung cancer (NSCLC), according to late-breaking results from the FLAURA trial presented today at the ESMO 2017 Congress in Madrid.
“EGFR mutations are present in around 15% of NSCLC in Western populations, rising to 35% in Asian populations. EGFR inhibitors are superior to chemotherapy in the first line treatment of these patients. However, despite high response rates and good progression-free survival, patients invariably develop resistance to drugs such as erlotinib and gefitinib. In the majority of patients this resistance is mediated by a T790M mutation.”