Prognostic role of PIK3CA and co-alterations in advanced biliary tract cancer: A multicenter retrospective analysis.

Biliary tract cancers (BTC) remain aggressive malignancies with limited treatment options. Alterations in are implicated in tumor progression across solid tumors, but their prognostic impact in BTC remains unclear. We investigated the association of alterations(alt), alone and in combination with and , with survival outcomes in advanced BTC. We conducted a retrospective analysis of 1,079 patients with advanced BTC treated with first-line chemotherapy (CT) or chemoimmunotherapy (CIO) across three sites in the USA, Japan, and Brazil. Genomic profiling was performed using next-generation sequencing on tissue and/or liquid biopsy samples. Survival outcomes were estimated by Kaplan-Meier analysis, with comparisons by log-rank testing and hazard ratios (HR) derived from Cox regression models. alterations were identified in 11% (123/1,079) of patients. The median age at diagnosis was 68 yrs (range, 20–79), with 50% (62/123) female. The most common primary site was intrahepatic in 43.1% (53/123) while majority of patients received CT only 92.5% (111/123). When analyzed with , 68 pts had co-alterations(co-alt), 501 had alt, 55 had alt alone, and 455 had neither nor alt (WT/WT). Overall survival (OS) was significantly worse in patients with alt, particularly in the setting of co-alt. Median OS (mOS) was 22.6 months(m) (95% CI, 20.4–24.8) for WT, 15.9 m (95% CI, 11.6–18.5) for alt WT, 14.6 m (95% CI, 13.1–19.5) for alt/ alt, and 17.1 m (95% CI, 15.5–18.8) for WT (p<0.001). In analyses with , 32 pts had co-alt, 91 had alt only, 120 had alt only, and 836 were WT/WT. co-alt tumors had a mOS of 12.8 m (95% CI, 9.1–NE) compared with 19.3 m (95% CI, 18.1–20.9) in WT WT (p=0.009). Multivariate analysis identified alt (hazard ratio [HR] 1.37, 95%CI 1.09–1.72; p=0.008), alt/ alt (HR 1.52 95% CI, 1.11–2.07; p=0.008), alt/ WT (HR 1.40, 95% CI 1.08-1.82, p=0.011), and metastatic status (HR 1.82, 95% CI 1.52-2.19, P<0.001) as independent prognostic factors for shorter OS. In advanced BTC, alt were associated with significantly worse overall survival, particularly when co-occurring with or alt. These findings establish as a prognostic biomarker of poor outcome and highlight the need to explore PI3K-targeted therapeutic strategies in BTC.

Duke Scholars

Author John Strickler Medicine, Medical Oncology