Roy S. Herbst, MD, PhD, cautioned that although FLAURA2 is a positive result, most patients will still develop drug resistance. “The result is really good and clearly positive, but if you look at the survival curves, there is still early overlap in a way that makes it unlikely this combination will show a survival benefit,” he explained. Dr. Herbst is Deputy Director of Yale Cancer Center; Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital; and Assistant Dean for Translational Research at Yale School of Medicine.
“There is no doubt you can improve progression-free survival with osimertinib and the combination of osimertinib plus chemotherapy, but giving additional chemotherapy to patients adds a lot of side effects in the absence of a survival benefit,” he continued.
Roy S. Herbst, MD, PhD
He pointed out that 40% of the study population had brain disease at baseline and that patients with L858R mutations did somewhat worse than those with exon 19 deletion.
“Osimertinib plus chemotherapy is probably not the standard of care for all patients. However, if it gets approved in this setting, I would consider using it in selected high-risk patients, including those with brain metastasis and perhaps certain specific EGFR mutations, after a discussion with patients about the risks and benefits. It is not going to become a de facto standard of care,” Dr. Herbst stated.
“The study speaks to the fact that better combinations are needed, for example, without chemotherapy. We need science to drive new ways to combine drugs to better combat primary and acquired resistance in this disease,” he concluded.
DISCLOSURE: Dr. Herbst has served on the board of directors of Immunocore and Junshi Biosciences; has received consulting fees from AstraZeneca, Bolt Biotherapeutics, Bristol Myers Squibb, Cancel Therapeutics, Checkpoint Therapeutics, Cybrexa Therapeutics, Dynamicure Biotechnology, eFFECTOR Therapeutics, Eli Lilly, EMD Serono, Genentech, Gilead Sciences, HiberCell, I-Mab Biopharma, Immune-Onc Therapeutics, Immunocore, Janssen, Johnson and Johnson, Loxo Oncology, Merck and Company, Mirati Therapeutics, NextCure, Novartis, Ocean Biomedical, Oncocyte Corp, Oncternal Therapeutics, Pfizer, Regeneron Pharmaceuticals, Revelar Biotherapeutics, Ribbon Therapeutics, Roche, Sanofi, and Xencor; and has received research funding from AstraZeneca, Eli Lilly, Genentech/Roche, and Merck and Company.
First-line treatment with osimertinib plus platinum-based chemotherapy achieved a statistically significant and clinically meaningful progression-free survival improvement compared with osimertinib alone in patients with advanced epidermal growth factor receptor (EGFR)-mutated non–small cell lung...