Pembrolizumab prolongs survival in persistent, recurrent, or metastatic cervical cancer

First results from KEYNOTE-826 showed that addition of pembrolizumab to chemotherapy ± bevacizumab significantly improved survival in patients with persistent, recurrent, or metastatic cervical cancer, regardless of PD-L1 expression.

Standard treatment for persistent, recurrent, or metastatic cervical cancer is platinum-based chemotherapy, with platinum, paclitaxel, and bevacizumab as a preferred regimen [1]. PD-L1 inhibitors have shown efficacy as monotherapy in previously treated patients with cervical cancer [2,3].

KEYNOTE-826 (NCT03635567) evaluated the efficacy and safety of pembrolizumab plus chemotherapy (plus bevacizumab at the investigators’ and patients’ discretion). Eligible patients had persistent, recurrent, or metastatic cervical cancer, were not amenable to curative treatment, and had not previously been treated with systemic chemotherapy (unless as part of chemoradiotherapy).

A total of 617 patients were randomised 1:1 to pembrolizumab (200 mg every 3 weeks for ≤35 cycles) or placebo added to 6 cycles of chemotherapy (paclitaxel plus cisplatin or carboplatin) ± bevacizumab (15 mg/kg every 3 weeks). Patients were stratified by metastatic status at diagnosis, planned bevacizumab use, and PD-L1 combined positive score (CPS). Of all patients enrolled, 51% were CPS ≥10, 38% were CPS 1–10, and 11% were CPS <1. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). First results of KEYNOTE-826 were presented by Prof. Nicoletta Colombo (Istituto Europeo di Oncologia, Italy) [4].

Addition of pembrolizumab to chemotherapy (± bevacizumab) significantly improved PFS and OS in the CPS ≥1, all-comer, and CPS ≥10 population. Median PFS was 10.4 months versus 8.2 months (CPS ≥1), 10.4 months versus 8.1 months (CPS ≥10), and 10.4 months versus 8.1 months (all-comers), compared with placebo. Median OS was not reached versus 16.3 months (CPS ≥1), not reached versus 16.4 months (CPS ≥10), and 24.4 months versus 16.5 months (all-comers), compared with placebo. The pembrolizumab benefit was seen regardless of bevacizumab use. Grade ≥3 adverse events incidence was 81.8% in the pembrolizumab plus chemotherapy arm and 75.1% in the placebo plus chemotherapy arm.

Based on these results, Prof. Colombo concluded that “pembrolizumab plus chemotherapy provided statistically significant and clinically meaningful improvement of both PFS and OS in patients with persistent, recurrent, or metastatic cervical cancer. Along with a manageable safety profile, these data suggest pembrolizumab plus chemotherapy may be a new standard of care for this population.”

1. Tewari KS, et al. N Engl J Med. 2014;370:734-743.
2. Chung HC, et al. J Clin Oncol. 2019;3:1470-1478.
3. Tewari KS, et al. EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9: Interim analysis of phase III trial of cemiplimab vs. investigator's choice (IC) chemotherapy (chemo) in recurrent/metastatic (R/M) cervical carcinoma. Abstract VP4-202, ESMO Congress 2021, 16–21 September.
4. Colombo N, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: randomized, double-blind, phase 3 KEYNOTE-826 study. Abstract LBA2, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November 202117 May 2024