|The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2021. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
The addition of pembrolizumab to platinum-based chemotherapy with or without bevacizumab prolonged survival compared with chemotherapy with or without bevacizumab among women with previously untreated advanced cervical cancer. These findings, from the phase 3 KEYNOTE-826 trial, were presented at the European Society for Medical Oncology (ESMO) Congress 2021 and simultaneously published in the New England Journal of Medicine.1,2
“Overall, data from KEYNOTE-826 suggests that pembrolizumab plus chemotherapy with or without bevacizumab may be a new standard of care for first-line treatment of persistent, recurrent, or metastatic cervical cancer,” Nicoletta Colombo, MD, of the University of Milan-Biocca and European Institute of Oncology in Italy said during her presentation.
The double-blind, phase 3 KEYNOTE-826 trial (ClinicalTrials.gov Identifier: NCT03635567) randomly assigned 617 patients with persistent, recurrent, or metastatic cervical cancer to receive pembrolizumab or matched placebo plus chemotherapy with or without bevacizumab. Chemotherapy comprised paclitaxel plus cisplatin or carboplatin. Prior systemic chemotherapy, unless prior to radiotherapy or as chemoradiotherapy, was not permitted.
The coprimary endpoints of the trial were progression-free survival (PFS) and overall survival (OS), which were tested sequentially among the PD-L1 combined positive score (CPS) ≥1, all-comer, and CPS ≥10 populations. Secondary endpoints included the objective response rate (ORR), duration of response (DOR), and safety. The presented results were of the first interim analysis with a median follow-up of 22 months.
The addition of pembrolizumab prolonged PFS in all populations. In the all-comer population, the median PFS was 10.4 months in the pembrolizumab group compared with 8.2 months in the placebo group (hazard ratio [HR], 0.65; 95% CI, 0.53-0.79; P <.001). These results were similar in the PD-L1 CPS ≥1 and ≥10 populations.
OS was also improved with the addition of pembrolizumab. In the all-comer population, the median was 24.4 months with pembrolizumab compared with 16.5 months with placebo (HR, 0.67; 95% CI, 0.54-0.84; P <.001). In the PD-L1 CPS ≥1 and ≥10 populations, the median OS was not reached in the pembrolizumab groups, compared with 16.3 months (HR, 0.64; 95% CI, 0.50-0.81; P <.001) and 16.4 months (HR, 0.61; 95% CI, 0.44-0.84; P =.001) with placebo.
ORR was higher with the addition of pembrolizumab and was similar among the populations, ranging from 65.9% to 69.6% compared with 49.1% to 50.8% with placebo. The median DOR was 18 months in the PD-L1 CPS 1 and all-comer populations and 21.1 months in the PD-L1 CPS ≥10 population with pembrolizumab, compared with 9.4 to 10.4 months in the placebo groups.
Treatment discontinuation due to treatment-related adverse events (TRAEs) occurred among 31.3% of patients in the pembrolizumab arms compared with 22.3% of patients in the placebo arms. Immune-mediated adverse events (irAEs) occurred among 33.9% and 15.2% of patients in the pembrolizumab and placebo arms, respectively. The most common irAEs were hypothyroidism, hyperthyroidism, and colitis.
Dr Colombo concluded that “adding pembrolizumab to chemotherapy with or without bevacizumab provides statistically significant, clinically meaningful improvements in PFS and OS in women with persistent, recurrent, or metastatic cervical cancer.”
Disclosures: This research was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: Randomized, double-blind, phase III KEYNOTE-826 study. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract LBA2_PR.
- Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. Published online September 18, 2021. doi:10.1056/NEJMoa2112435