Efficacy and safety of immune checkpoint inhibitors combined with TKIs for recurrent or metastatic cervical cancer with PIK3CA mutation

Background PIK3CA mutations are among the most common driver mutations in cervical cancer (CC), yet therapeutic strategies targeting PIK3CA mutations are still under investigation. This study aims to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs) in patients with PIK3CA-mutated recurrent or metastatic (R/M) CC. Methods This study was based on two prospective clinical trials (ChiCTR1900023015 and the CLAP study) and retrospective data from Fujian Cancer Hospital, comparing ICIs combined with TKIs with physician’s-choice Non-ICI/TKI conventional treatments in PIK3CA-mutated R/M CC. The primary endpoint was objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results A total of 55 patients were included, with 27 in the ICIs plus TKIs treatment group and 28 in the Non-ICI/TKI conventional treatment group. The ORR in the ICIs plus TKIs group was 85.19% (95% CI, 67.52%−94.08%), significantly higher than 28.57% (95% CI, 15.25%−47.06%) in the Non-ICI/TKI conventional treatment group (P < 0.001). The PFS in the ICIs plus TKIs group was 21.03 months, significantly longer than 9.13 months in the Non-ICI/TKI conventional treatment group (HR, 0.49; 95% CI, 0.26–0.94, P = 0.033). Although the OS difference was not statistically significant (HR, 0.65; 95% CI, 0.31–1.34, P = 0.24), the ICIs plus TKIs group showed superior clinical efficacy. The incidence of hypertension (P < 0.001), rash (P = 0.004), hypothyroidism (P < 0.001), proteinuria (P = 0.010), and palmoplantar erythrodysesthesia syndrome (P = 0.023) was higher in the ICIs plus TKIs group compared to the Non-ICI/TKI conventional treatment group. The observed adverse events were generally manageable. Although grade ≥3 adverse events occurred, no grade ≥3 immune-related adverse events or treatment-related deaths were observed. Conclusion ICIs plus TKIs demonstrated significant efficacy in treating PIK3CA-mutated R/M CC. Although there were some safety concerns, the adverse reactions were manageable, no grade ≥3 immune-related adverse events or treatment-related deaths were observed.