Impact of Concurrent PIK3CA Mutations on Response to EGFR Tyrosine Kinase Inhibition in EGFR-Mutant Lung Cancers and on Prognosis in Oncogene-Driven Lung Adenocarcinomas

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Juliana EngAlexander Drilon

Abstract

In patients with epidermal growth factor receptor (EGFR)-mutant or KRAS-mutant lung adenocarcinomas, the prognostic impact of a concurrent PIK3CA mutation remains unclear. Although preclinical data suggest that sensitivity to EGFR tyrosine kinase inhibition (TKI) is decreased in EGFR-mutant lung cancers also harboring a PIK3CA mutation, this interaction has not been explored clinically. Patients with lung adenocarcinomas harboring a PIK3CA mutation concurrent with a separate driver mutation were identified through mutational hotspot testing, multiplex sizing assays, and fluorescence in situ hybridization. Overall survival and outcomes with EGFR TKI monotherapy (EGFR-mutant) were estimated using Kaplan-Meier methods and compared between double-mutant (EGFR-mutant or KRAS-mutant, concurrent PIK3CA-mutant) and single-mutant patients (EGFR-mutant or KRAS-mutant, PIK3CA wild-type) using log-rank tests. In EGFR-mutant and KRAS-mutant lung cancers, a concurrent PIK3CA mutation was associated with a decrease in median overall survival: 18 versus 33 months (EGFR double mutant, n = 10 versus single mutant, n = 43, p = 0.006), and 9 versus 16 months (KRAS double mutant, n = 16 versus single mutant, n = 47, p = 0.020). In EGFR-mutant lung ...Continue Reading

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Citations

Aug 16, 2016·Surgical Pathology Clinics·Lynette M Sholl
Feb 13, 2017·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Nicolas GuibertJulien Mazières
Apr 7, 2017·The European Respiratory Journal·Olivier CalvayracNicolas Guibert
Jun 9, 2020·Clinical and Translational Medicine·Mengjia QianYunfeng Cheng
Aug 10, 2018·JCI Insight·Suchita Pakkala, Suresh S Ramalingam
Nov 21, 2017·NPJ Precision Oncology·Dana S Neel, Trever G Bivona
Aug 14, 2019·Nature Reviews. Cancer·Ferdinandos Skoulidis, John V Heymach
Oct 1, 2019·British Journal of Cancer·Alessandro LeonettiMarcello Tiseo
Nov 1, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matteo CanalePaola Ulivi
Sep 20, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiuning LeJohn V Heymach
Feb 6, 2021·Clinical Chemistry and Laboratory Medicine : CCLM·Pamela PinzaniSilvia Galbiati
Mar 15, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Philippe JammeAlexis B Cortot
Apr 13, 2021·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Daryn GoodwinGavin M Wright

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