Pembrolizumab plus chemotherapy as a new standard of care for women with persistent, recurrent or metastatic cervical cancer

Final overall survival (OS) results of the phase III Keynote-826 trial further solidify the addition of pembrolizumab to chemotherapy, with or without bevacizumab as standard of care in the first-line treatment of women with persistent, recurrent or metastatic cervical cancer. In this trial, the addition of pembrolizumab to chemotherapy resulted in a significantly longer overall survival, regardless of the level of PD-L1 expression.

Platinum-based chemotherapy is the standard treatment for persistent, recurrent or metastatic cervical cancer. In addition, pembrolizumab monotherapy has shown efficacy in previously treated cervical cancer. In Keynote-826, the addition of pembrolizumab to chemotherapy, with or without bevacizumab, provided statistically significant, clinically meaningful overall survival (OS) and progression-free survival (PFS) improvements and was generally well tolerated in patients with persistent, recurrent or metastatic cervical cancer. At ASCO 2023, Dr. Monk presented the protocol-specified final OS results of Keynote-826.

Study design

Keynote-826 is an international, randomised, double-blind phase III study that enrolled 617 patients with persistent, recurrent or metastatic cervical cancer not amenable to curative treatment. Patients were not allowed to have received prior systemic chemotherapy (prior radiotherapy and chemoradiotherapy was permitted). All women had an ECOG performance status of 0 or 1. Participants were randomised in a 1:1 ratio to pembrolizumab (200 mg) or placebo every 3 weeks (Q3W) for up to 35 cycles plus platinum-based chemotherapy (paclitaxel plus cisplatin or carboplatin Q3W for up to six cycles) and, per investigator discretion, bevacizumab (15 mg/kg, IV Q3W). Patients were stratified based on metastatic disease at diagnosis (yes vs. no), PD-L1 CPS (<1 vs. 1 to <10 vs. ≥10) and planned bevacizumab use (yes vs. no). Dual primary endpoints are OS and PFS per RECIST v.1.1 by investigator.

Results

After a median follow-up of 39.1 months, the addition of pembrolizumab to chemotherapy with or without bevacizumab resulted in a 40% difference in OS (HR[95%CI]: 0.60[0.49-0.74], p< 0.0001) in patients with PD-L1 CPS ≥1. Median OS was 28.6 months for patients in the pembrolizumab arm, as compared to 16.5 months for patients in the placebo-arm. The 24-month OS rates were respectively 53.5% and 39.4%. For patients with a PD-L1 CPS ≥10, median OS was 29.6 months in the pembrolizumab group vs. 17.4 months in the placebo group. Finally, in the all-comer population, the risk of death was reduced by 37% (HR[95%CI]: 0.63[0.52-0.77], p< 0.0001) with a median OS of 26.4 months for patients receiving pembrolizumab and 16.8 months for patients in the control arm. PFS was 10.4 months in the pembrolizumab group vs. 8.2 months in the placebo group for all participants (HR[95%CI]: 0.61[0.-0.74], p< 0.0001). Importantly, the benefit of pembrolizumab was consistent across all protocol-specified subgroups, including the with and without bevacizumab subgroups. Furthermore, the objective response rate was higher and the duration of response was longer with the addition of pembrolizumab.

The safety profile of the combination regimen was manageable and observed adverse events (AEs) were as expected based on the profiles of the individual drugs. The most common grade 3 or higher AEs in the pembrolizumab group vs. the placebo group were anemia (30.3% vs. 27.8%), neutropenia (12.4% vs. 9.7%), and hypertension (10.4% vs. 11.7%). There were no new safety-signals reported after longer follow-up.

Conclusion

At the protocol-specified final analysis of Keynote-826, the addition of pembrolizumab to chemotherapy with or without bevacizumab continued to show substantial and clinically meaningful OS and PFS improvements in women with persistent, recurrent or metastatic cervical cancer.  Findings are consistent with the previous interim data and provide further support for first-line pembrolizumab plus chemotherapy, with or without bevacizumab, as a new standard of care for women with persistent, recurrent or metastatic cervical cancer.

Reference

Monk BJ, et al. KEYNOTE-826: Final overall survival results from a randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for first-line treatment of persistent, recurrent, or metastatic cervical cancer. Presented at ASCO 2023; Abstract 5500.