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J Thorac Oncol. 2015 Dec;10(12):1713-9. doi: 10.1097/JTO.0000000000000671.

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.

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*Thoracic Oncology Service, Department of Medicine, †Department of Epidemiology and Biostatistics, ‡Department of Radiology, and §Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY.



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 cancers, a concurrent PIK3CA mutation did not impact benefit from EGFR TKI monotherapy. Single versus double mutant: objective response rate, 83% (n = 29) versus 62% (n = 6, p = 0.80); median time to progression, 11 (n = 29) versus 8 months (n = 6, p = 0.84); and median duration of TKI therapy, 15 (n = 32) versus 15 months (n = 10, p = 0.65).


A concurrent PIK3CA mutation is a poor prognostic factor in patients with advanced EGFR-mutant or KRAS-mutant lung adenocarcinomas. There was no evidence that clinical benefit from EGFR TKI monotherapy is affected by a concurrent PIK3CA mutation in EGFR-mutant lung cancers.

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