Efficacy and safety of immune checkpoint inhibitors combined with TKIs for recurrent or metastatic cervical cancer with PIK3CA mutation: A secondary analysis based on two prospective studies.

e17516 Background: PIK3CA gene 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, providing a new treatment option for this patient group. Methods: This study is based on two prospective clinical trials (ChiCTR1900023015 and the CLAP study) and retrospective control data from Fujian Cancer Hospital, comparing the efficacy of ICIs combined with TKIs versus 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 conventional treatment group. The ORR in the ICIs plus TKIs group was 85.19%, significantly higher than 28.57% in the conventional treatment group (P<0.01). The PFS in the ICIs plus TKIs group was 21.03 months, significantly longer than 9.13 months in the conventional treatment group (P=0.033). Although the OS difference was not statistically significant (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=0.007), and palmoplantar erythrodysesthesia syndrome (P=0.023) was higher in the ICIs plus TKIs group compared to the conventional treatment group. All adverse events were manageable, and no severe adverse events or treatment-related deaths were observed. Conclusions: ICIs combined with TKIs demonstrated significant efficacy in treating PIK3CA-mutated R/M CC, particularly in prolonging PFS and improving the ORR. Although there are some safety concerns, the adverse reactions were manageable, with no severe treatment-related adverse events observed. This combination therapy may represent a promising new treatment option for R/M CC.