Background
Double-blind phase 3 trial (KEYNOTE-826) of 617 patients (548 with PD-L1 CPS ≥1) with persistent, recurrent, or metastatic cervical cancer not previously treated with chemotherapy and not amenable to curative treatment. Evaluated adding pembrolizumab to platinum chemotherapy with or without bevacizumab.
Interventions and follow up
Arm A: Pembrolizumab 200 mg IV every 3 weeks up to 35 cycles + platinum chemotherapy ± bevacizumab*
Arm B: Placebo + platinum chemotherapy ± bevacizumab*
Primary endpoints: PFS and OS (in CPS ≥1, all-comer, and CPS ≥10 populations)
Regimen detail: *Paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5 q3wk; bevacizumab 15 mg/kg q3wk at investigator discretion
mFollow up: 22 mo
Arm B: Placebo + platinum chemotherapy ± bevacizumab*
Primary endpoints: PFS and OS (in CPS ≥1, all-comer, and CPS ≥10 populations)
Regimen detail: *Paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5 q3wk; bevacizumab 15 mg/kg q3wk at investigator discretion
mFollow up: 22 mo
Results
mPFS (CPS ≥1): 10.4 mo vs 8.2 mo; HR 0.62, 95%CI 0.50-0.77, P<.001
2-yr OS (CPS ≥1): 53.0% vs 41.7%; HR 0.64, 95%CI 0.50-0.81, P<.001
OS (all-comers): HR 0.67, 95%CI 0.54-0.84, P<.001
2-yr OS (CPS ≥1): 53.0% vs 41.7%; HR 0.64, 95%CI 0.50-0.81, P<.001
OS (all-comers): HR 0.67, 95%CI 0.54-0.84, P<.001
Adverse events
Overall grade ≥3: 81.8% vs 75.1% (pembrolizumab vs placebo)
Hematologic/GI (any grade): anemia 61.2% vs 53.4%, nausea 39.7% vs 43.7%, diarrhea 35.5% vs 29.8%, neutropenia common in both arms
Other (any grade): alopecia 56.4% vs 57.9%, fatigue, peripheral neuropathy, hypertension, arthralgia; immune-mediated events more frequent with pembrolizumab
Hematologic/GI (any grade): anemia 61.2% vs 53.4%, nausea 39.7% vs 43.7%, diarrhea 35.5% vs 29.8%, neutropenia common in both arms
Other (any grade): alopecia 56.4% vs 57.9%, fatigue, peripheral neuropathy, hypertension, arthralgia; immune-mediated events more frequent with pembrolizumab
Conclusions
Adding pembrolizumab to platinum-based chemotherapy with or without bevacizumab significantly prolonged PFS and OS in persistent, recurrent, or metastatic cervical cancer, with benefit most pronounced in PD-L1 CPS ≥1 tumors.
Key Limitations
Benefit concentrated in PD-L1-positive tumors; PD-L1-negative subgroup too small for firm conclusions. Bevacizumab use was non-randomized (investigator choice), confounding regimen comparison.
Clinical Context
Supported FDA approval (Oct 2021, expanded 2024) of pembrolizumab with chemotherapy ± bevacizumab for persistent/recurrent/metastatic cervical cancer; ESMO recommends pembrolizumab plus platinum chemotherapy as preferred first-line therapy for PD-L1 CPS ≥1 disease.