Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study

HIGHLIGHTS•This exploratory analysis of KEYNOTE-826 examined treatment outcomes in patient subgroups defined by bevacizumab (beva) use•Pembrolizumab+chemotherapy improved progression-free survival and overall survival vs placebo+chemotherapy in all subgroups•The safety profile of pembrolizumab+chemotherapy±beva was manageable•Results support use of pembrolizumab+chemotherapy±beva for persistent, recurrent, or metastatic cervical cancerABSTRACTBackgroundIn KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (± bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use.Patients and methodsEligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1:1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (± bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% CIs were based on a stratified Cox regression model.Results617 patients were randomized (pembrolizumab arm, n=308 [63.6% with bevacizumab]; placebo arm, n=309 [62.5% with bevacizumab]). The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the PD-L1 combined positive score (CPS) ≥1 (0.56 [0.43−0.73]) and all-comer (0.57 [0.45−0.73]) populations; OS results were 0.60 (0.45−0.79) and 0.61 (0.47−0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the PD-L1 CPS≥1 (0.61 [0.44−0.85]) and all-comer (0.69 [0.50−0.94]) populations; OS results were 0.61 (0.44−0.85) and 0.67 (0.49−0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm.ConclusionPembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.