Abstract
BACKGROUND: Platinum-resistant recurrent ovarian cancer remains a major therapeutic challenge. Immune checkpoint inhibitors (ICIs) combined with chemotherapy are widely used, but clinical benefits remain limited. Thymosin α1 (Tα1), an immunomodulatory peptide, may synergize with ICIs to enhance anti-tumor immunity. METHODS: This retrospective study included 386 patients with PROC, with 193 patients receiving Tα1 combined with PD-1/PD-L1 inhibitors and chemotherapy (experimental group), and 193 patients receiving PD-1/PD-L1 inhibitors and chemotherapy alone (control group). Baseline clinical characteristics, clinical efficacy, immune parameters, progression-free survival (PFS), and adverse events were compared between the two groups. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression were used to assess PFS and associated prognostic factors. Continuous and categorical variables were compared using t-test and χ(2) -test, respectively. Statistical significance was defined as p < 0.05. RESULTS: Baseline characteristics were comparable between the two groups. The experimental group showed significantly higher objective response rate (43% vs 30.2%; p = 0.008) and disease control rate (87% vs 69.8%; p = 0.000). The median PFS was significantly longer in the experimental group (3.0 vs 1.1 months; HR = 3.22, 95% CI: 2.59-4.01; p = 0.000). Post-treatment, patients in the experimental group demonstrated significantly elevated levels of IgA, IgG, IgM, CD3(+), CD4(+), CD4(+)/CD8(+) ratio, and NK cells compared to the control group (all p < 0.01), while CD8 levels remained similar. The incidence of adverse events was lower in the experimental group (50.8% vs 65.8%; χ(2) = 8.35, p = 0.004), primarily due to a reduced rate of myelosuppression. CONCLUSION: The addition of Tα1 to PD-1/PD-L1 inhibitor-based chemotherapy may enhance treatment efficacy, improve immune response, and reduce immunosuppression-related toxicity in patients with platinum-resistant recurrent ovarian cancer.