Invited discussant Nicolas Girard, MD, PhD, of the Curie Institute, Paris, said, “A major challenge in NSCLC is what happens when osimertinib resistance develops.”

Nicolas Girard, MD, PhD

“A key takeaway point from this study is that the efficacy is driven by resistance mechanism. The overall response rate was 47% in the EGFR/MET-based resistance group, but looking deeper at the data, we have a 75% response in the purely MET-driven resistance mechanism group and 27% in the purely EGFR-driven resistance mechanism group. The group of patients without EGFR/MET-based resistance is heterogeneous. We have no response in the EGFR/MET-independent resistant patients,” Dr. Girard continued.

Dr. Girard noted that preliminary evidence suggests that the combination has a prolonged duration of response and said that duration of response according to resistance mechanism should be explored. “The rate of progression-free survival in the whole population was disappointing, and selection of patients based on resistance mechanisms is warranted,” he noted.

“One of the clinical challenges is the feasibility of rebiopsy. The IHC data seem to be highly predictive of response,” he added.

DISCLOSURE: Dr. Girard has an immediate family member who has been employed by AstraZeneca; has served in a consulting or advisory role for AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Hoffman La Roche, Janssen, Lilly, MSD, Novartis, Pfizer, Pharmamar, Sanofi, and Takeda; received institutional research funding from AstraZeneca, Boehringer Ingelheim.