That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.
The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.
The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.
“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.
Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.
Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.
Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.
“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”
KEYNOTE-826 details
This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.
The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.
Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).