Pembrolizumab plus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer: Subgroup analysis of KEYNOTE-826.

5506 Background: In KEYNOTE-826 (NCT03635567),pembrolizumab (pembro) + chemotherapy (chemo) ± bevacizumab (bev) provided statistically significant, clinically meaningful PFS and OS improvements in patients with persistent, recurrent, or metastatic cervical cancer. In the present analysis of KEYNOTE-826, we assessed outcomes in several key patient subgroups. Methods: Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemo and not amenable to curative treatment; measurable disease per RECIST v1.1; ECOG PS 0–1; and a tumor sample to determine PD-L1 status. Patients were randomized 1:1 to pembro 200 mg Q3W or placebo (pbo) for up to 35 cycles + chemo (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) ± bev 15 mg/kg. Dual primary endpoints are PFS by investigator assessment per RECIST v1.1 and OS in patients with PD-L1 CPS ≥1, all comers, and CPS ≥10. Treatment effects on PFS and OS were examined in patient subgroups defined by bev use (yes or no), histology (squamous or non-squamous [including adenocarcinoma and adenosquamous]), platinum use (carboplatin or cisplatin), and prior chemoradiation therapy (CRT). Hazard ratios (HR) and 95% CIs were based on a stratified Cox regression model. Results: 617 patients were randomized (pembro + chemo ± bev, n=308; pbo + chemo ± bev, n=309). At the May 3, 2021 data cutoff, median follow-up was 22 months. Pembro + chemo prolonged PFS and OS vs pbo + chemo in all subgroups evaluated in the all-comer population (Table). Similar benefits of pembro + chemo on PFS and OS were also seen in the protocol-specified CPS ≥1 and CPS ≥10 populations. Conclusions: Pembro + chemo ± bev prolonged PFS and OS vs pbo + chemo ± bev among the subgroups defined by bev use, histology, platinum use, and prior CRT and provided clinically meaningful benefits similar to the broader population of patients with persistent, recurrent, or metastatic cervical cancer. Clinical trial information: NCT03635567. [Table: see text]