Dr Garon on Challenges Associated With Immunotherapy Use in EGFR-mutated NSCLC

Edward B. Garon, MD, MS, professor of medicine, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, the University of California, Los Angeles (UCLA), UCLA Health, discusses challenges associated with the incorporation of immunotherapy into the treatment paradigm for EGFR-mutant non–small cell lung cancer (NSCLC).

Attempts to incorporate immunotherapy approaches into the treatment landscape for patients with EGFR-mutant NSCLC have been met with several challenges, Garon begins. Historically, response rates with single-agent PD-1/PD-L1 inhibitors in this population have been low, he says. Despite some encouraging early data, efforts to improve sensitivity to such approaches using CTLA-4 inhibition have not shown conclusive success, Garon states.

In a study of frontline immunotherapy approaches conducted by Aaron Lisberg, MD, of UCLA, patients who received an EGFR inhibitor following treatment with a PD-1 inhibitor did not experience sufficient benefit, Garon continues. Moreover, these patients also experienced high toxicities.

Conversely, the efficacy of angiogenesis inhibition plus PD-1 or PD-L1 inhibition and chemotherapy in this population has been demonstrated by 2 key trials, Garon reports. The phase 3 IMpower150 trial (NCT02366143) of atezolizumab (Tecentriq) plus bevacizumab (Avastin), carboplatin, and paclitaxel demonstrated improved overall survival with the experimental combination vs bevacizumab and chemotherapy in patients with metastatic nonsquamous NSCLC. Based on these results, a replication study was conducted by a group in China to evaluate a PD-1 inhibitor plus a biosimilar of the antiangiogenic agent.

As data from these trials continue to mature, researchers may identify biomarkers that are predictive of patient benefit, Garon says. This would allow for improved selection of patients with EGFR mutations for immunotherapy regimens, he concludes.

Disclosures: Dr Garon has reported consulting or advisory roles with AbbVie, ABL-Bio, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Ipsen, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, and Xilio; and has received grant/research support from ABL-Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis.