Anti-PD-1 therapy plus chemotherapy versus anti-PD-1 therapy alone in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia: a multicenter, retrospective study.

Background: Synergistic antitumor effects of immunotherapy and chemotherapy have been demonstrated in several solid tumors. However, this combination strategy has not been addressed in gestational trophoblastic neoplasia (GTN) cases. We therefore compared the safety and therapeutic effect of anti-programmed cell death 1 (PD-1) therapy combined with chemotherapy versus anti-PD-1 monotherapy among high-risk chemorefractory or relapsed GTN patients. Methods: This retrospective cohort study was conducted at three teaching hospitals in China. Chemorefractory or relapsed GTN cases receiving anti-PD-1 therapy combined with chemotherapy or anti-PD-1 monotherapy were selected from each center between August 2018 and March 2022. Study endpoints included objective response rate (ORR), treatment duration, overall survival (OS) and progression-free survival (PFS). The nature, prevalence and severity of treatment-related adverse events (TRAEs) were evaluated. Findings: This work enrolled 66 cases. Thirty-five and 31 patients received anti-PD-1 therapy alone and combined with chemotherapy, respectively. The combined treatment dramatically increased the objective response rate from 62.9% (22/35) to 96.8% (30/31) (p < 0.001). The median durations until complete response were 2.2 (interquartile range [IQR], 1.4-4.2) and 2.8 (IQR, 1.8-2.8) months in the anti-PD-1 monotherapy and combined treatment cohorts, respectively (P = 0.299). The complete response rate (CRR) for anti-PD-1-refractory patients to salvage chemotherapy was 84.6% (11/13). No significant difference in OS [HR 0.50 (95% CI 0.07-3.24), p = 0.499] was detected between anti-PD-1 cohort and anti-PD-1 plus chemotherapy cohort. The PFS in combined group was significantly longer than in anti-PD-1 group [HR 0.06 (95% CI 0.02-0.16), p < 0.001]. TRAEs were observed in 27 (77.1%) and 25 (80.6%) patients receiving anti-PD-1 therapy monotherapy and combined therapy, respectively (p = 0.729). Interpretation: Anti-PD-1 therapy combined with chemotherapy exhibits sustainably improved antitumor effect and tolerable toxic effects among high-risk chemorefractory or relapsed GTN cases. Patients not responding to PD-1 inhibitors can be effectively rescued with salvage chemotherapy. Funding: The study was supported by National Natural Science Foundation of China (81971475 and 81972451), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-083 and 2022-PUMCH-B-084).