*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.
J Thorac Oncol. 2015 Dec;10(12):1713-9. doi: 10.1097/JTO.0000000000000671.
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.
在表皮生长因子受体（EGFR）突变或 KRAS 突变的肺腺癌患者中，同时存在 PIK3CA 突变的预后影响尚不清楚。尽管临床前数据表明，同时存在 PIK3CA 突变的 EGFR 突变型肺癌对 EGFR 酪氨酸激酶抑制剂（TKI）的敏感性降低，但这种相互作用尚未在临床上得到探索。
通过突变热点检测、多重定序分析和荧光原位杂交，鉴定出同时存在 PIK3CA 突变的肺腺癌患者。使用 Kaplan-Meier 方法估计携带 EGFR TKI 单药治疗（EGFR 突变）的总生存期，并使用对数秩检验比较双突变（EGFR 突变或 KRAS 突变，同时存在 PIK3CA 突变）和单突变患者（EGFR 突变或 KRAS 突变，PIK3CA 野生型）的结果。
在 EGFR 突变和 KRAS 突变的肺癌中，同时存在 PIK3CA 突变与中位总生存期的降低相关：18 个月与 33 个月（EGFR 双突变，n=10 与单突变，n=43，p=0.006），9 个月与 16 个月（KRAS 双突变，n=16 与单突变，n=47，p=0.020）。在 EGFR 突变的肺癌中，同时存在 PIK3CA 突变并不影响 EGFR TKI 单药治疗的获益。单突变与双突变：客观缓解率，83%（n=29）与 62%（n=6，p=0.80）；中位无进展生存期，11 个月（n=29）与 8 个月（n=6，p=0.84）；以及 EGFR TKI 治疗的中位持续时间，15 个月（n=32）与 15 个月（n=10，p=0.65）。
在晚期 EGFR 突变或 KRAS 突变的肺腺癌患者中，同时存在 PIK3CA 突变是一个预后不良的因素。在 EGFR 突变的肺癌中，没有证据表明同时存在 PIK3CA 突变会影响 EGFR TKI 单药治疗的临床获益。
