Invited discussant of the abstract, Joel W. Neal, MD, PhD, Associate Professor of Medicine at Stanford University, called this real-world analysis novel,1 given the decreasing number of patients treated with single-agent immunotherapy.
“I think we’re unlikely to have a larger prospective study [in this setting] because we seldom use single-agent immune checkpoint inhibitors anymore, and for patients with ALK and ROS1 mutations, we tend to avoid them based on prior data showing very low response rates,” said Dr. Neal.
He also highlighted the better performance of patients with BRAF- and KRAS-mutated tumors. “It’s clear that patients with BRAF and KRAS mutations do the best. Approximately 10% or more of these patients are still alive without disease progression on single-agent immunotherapy, whereas most of the patients with EGFR and ALK mutations had disease progression by this point.”
Joel W. Neal, MD, PhD
For patients with EGFR- and ALK-positive tumors, however, Dr. Neal underscored the potential correlation between smoking history and response. “There aren’t that many patients with ALK-positive or EGFR-mutant lung cancer who have a heavy smoking history, but there is a significant difference in their response to immunotherapy,” he observed. “I’d be curious about the response to ALK inhibitors for the ALK-positive patients who responded to immunotherapy with a smoking history.”
Finally, based on these data, Dr. Neal acknowledged doubts about whether PD-L1 expression is a predictive marker in EGFR-mutant lung cancer. “I often use it clinically but now wonder about the strength of its predictive value,” he concluded.
DISCLOSURE: Dr. Neal has received honoraria from Research to Practice, MLI Peerview, Medscape, Biomedical Learning Institute, Prime Oncology, Rockpointe, CME Matters, and MJH CME; served as a consultant or advisor to AstraZeneca, Genentech/Roche, Exelixis, Jounce Therapeutics, Takeda Pharmaceuticals, Loxo/Eli Lilly, Calithera Biosciences, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, and Regeneron; has received research funding from Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Takeda Pharmaceuticals, Nektar Therapeutics, Adaptimmune, and GSK; and has received royalties from Up to Date.
REFERENCE
1. Neal JW: Novel, novel-er, and novel-est targets in NSCLC. 2020 North America Conference on Lung Cancer. Oral Abstract Session 2. Presented October 17, 2020.
