journal contribution posted on 2023-06-01, 08:20 authored by Michael J. Grant, Jacqueline V. Aredo, Jacqueline H. Starrett, Paul Stockhammer, Iris K. van Alderwerelt van Rosenburgh, Anna Wurtz, Andrew J. Piper-Valillo, Zofia Piotrowska, Christina Falcon, Helena A. Yu, Charu Aggarwal, Dylan Scholes, Tejas Patil, Christina Nguyen, Manali Phadke, Fang-Yong Li, Joel Neal, Mark A. Lemmon, Zenta Walther, Katerina Politi, Sarah B. Goldberg
Supplementary Figure S1. Multi-institution cohort of patients with tumors harboring EGFR Exon 19 deletions. Primary analyses were performed on patients with tumors harboring E746_A750del and L747_A750>P, while investigation into additional uncommon variants was descriptive only. Patient numbers do not reflect the true prevalence of each variant since this cohort is selectively enriched for uncommon exon 19 deletions.
Yale SPORE in Lung Cancer
National Institutes of Health (NIH)
Yale Cancer Center
American Society of Clinical Oncology (ASCO)
Conquer Cancer Foundation (CCF)
ARTICLE ABSTRACTThe uncommon EGFR exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared with the common ex19del, E746_A750del in preclinical models. The clinical efficacy of osimertinib in patients with non–small cell lung cancer harboring L747_A750>P and other uncommon ex19dels is not known.
The AACR GENIE database was interrogated to characterize the frequency of individual ex19dels relative to other variants, and a multicenter retrospective cohort was used to compare clinical outcomes for patients with tumors harboring E746_A750del, L747_A750>P, and other uncommon ex19dels who received osimertinib in the first line (1L) or in second or later lines of therapy and were T790M+ (≥2L).
ex19dels comprised 45% of EGFR mutations, with 72 distinct variants ranging in frequency from 28.1% (E746_A750del) to 0.03%, with L747_A750>P representing 1.8% of the EGFR mutant cohort. In our multi-institutional cohort (N = 200), E746_A750del was associated with significantly prolonged progression-free survival (PFS) with 1L osimertinib versus L747_A750>P [median 21.3 months (95% confidence interval, 17.0–31.7) vs. 11.7 months (10.8–29.4); adjusted HR 0.52 (0.28–0.98); P = 0.043]. Osimertinib efficacy in patients with other uncommon ex19dels varied on the basis of the specific mutation present.
The ex19del L747_A750>P is associated with inferior PFS compared with the common E746_A750del mutation in patients treated with 1L osimertinib. Understanding differences in osimertinib efficacy among EGFR ex19del subtypes could alter management of these patients in the future.