| Autor: |
Sarah B. Goldberg, Katerina Politi, Zenta Walther, Mark A. Lemmon, Joel Neal, Fang-Yong Li, Manali Phadke, Christina Nguyen, Tejas Patil, Dylan Scholes, Charu Aggarwal, Helena A. Yu, Christina Falcon, Zofia Piotrowska, Andrew J. Piper-Valillo, Anna Wurtz, Iris K. van Alderwerelt van Rosenburgh, Paul Stockhammer, Jacqueline H. Starrett, Jacqueline V. Aredo, Michael J. Grant |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6604893.v1 |
| Popis: |
Purpose:The 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.Design: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).Results: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.Conclusions: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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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