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 Article
| Authors: | Eng, J.; Woo, K. M.; Sima, C. S.; Plodkowski, A.; Hellmann, M. D.; Chaft, J. E.; Kris, M. G.; Arcila, M. E.; Ladanyi, M.; Drilon, A. |
| Article Title: | 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 |
| Abstract: | Introduction: 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. Methods: 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. Results: 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). Conclusion: 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. © 2015 by the International Association for the Study of Lung Cancer. |
| Keywords: | tyrosine kinase inhibitors; pik3ca mutation; egfr-mutant lung adenocarcinomas |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 10 |
| Issue: | 12 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2015-12-01 |
| Start Page: | 1713 |
| End Page: | 1719 |
| Language: | English |
| DOI: | 10.1097/jto.0000000000000671 |
| PROVIDER: | scopus |
| PUBMED: | 26334752 |
| PMCID: | PMC4760768 |
| DOI/URL: | |
| Notes: | Export Date: 2 December 2015 -- Source: Scopus |
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