Adding the immunotherapy drug pembrolizumab to chemotherapy, with or without bevacizumab, improved overall survival (OS) and progression-free survival (PFS) in people with persistent, recurrent, or metastatic cervical cancer, regardless of whether the cancer expressed PD-L1.
The research will be presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
Study participants were randomly assigned to receive either pembrolizumab with chemotherapy or placebo with chemotherapy, with or without bevacizumab.
At a median follow-up of 39.1 months, the combination of pembrolizumab with chemotherapy improved both OS and PFS in all participants, regardless of PD-L1 expression and whether bevacizumab was received.
These long-term follow-up results support earlier findings from the study.
OS was 28.6 months in the pembrolizumab group vs. 16.5 months in the placebo group for those with a PD-L1 combined positive score of 1 or higher, 29.6 months vs. 17.4 months for those with a PD-L1 combined positive score of 10 or higher, and 26.4 months vs. 16.8 months for all participants.
PFS was 10.4 months in the pembrolizumab group vs. 8.2 months in the placebo group for all participants.
The combination of pembrolizumab with chemotherapy reduced the risk of death by 40% in patients with a PD-L1 combined positive score of 1 or higher, by 42% in patients with a PD-L1 combined positive score of 10 or higher, and by 37% in all patients.
Grade 3 or higher adverse events were more common in the pembrolizumab group, with 82.4% of participants experiencing events vs. 75.4% of those in the placebo group.
The most common grade 3 or higher adverse effects in the pembrolizumab group vs. the placebo group were anaemia (30.3% vs. 27.8%), neutropenia (12.4% vs. 9.7%), and hypertension (10.4% vs. 11.7%).
“Before KEYNOTE-826, the standard of care was a platinum-based paclitaxel chemotherapy combination with or without bevacizumab treatment for people with this diagnosis,” said lead author Bradley J. Monk, MD, FACS, FACOG, Professor in the Division of Gynecologic Oncology at Creighton University School of Medicine, HonorHealth Research Institute in Phoenix, Arizona.
“This study demonstrates that giving immunotherapy earlier provides a substantial overall survival benefit compared with the second-line setting. Our results also show a survival benefit of pembrolizumab in patients who are not eligible for bevacizumab, offering a therapeutic option in this population of patients with a high unmet need.”
In the United States, about 16% of people with cervical cancer are diagnosed with metastatic disease.
The 5-year relative survival rate for people with metastatic cervical cancer in the U.S. is 17%.
Worldwide, cervical cancer is the fourth most commonly diagnosed cancer and fourth most common cause of cancer death in women.
Pembrolizumab is a type of immunotherapy called an immune checkpoint inhibitor that works by targeting the PD-1 protein found on the surface of T cells. Since PD-1 stops the immune system from destroying cancer cells, targeting PD-1 can help the immune system better destroy the cancer. Some cancer cells express the PD-L1 protein, which binds to the PD-1 protein on T cells.
Pembrolizumab is currently approved by the U.S. Food and Drug Administration in combination with chemotherapy, with or without bevacizumab, to treat persistent, recurrent, or metastatic cervical cancer that expresses PD-L1.
This study shows that the addition of pembrolizumab to chemotherapy could be an effective first-line treatment option for people with this diagnosis regardless of whether the cancer expresses PD-L1.
About the Study
The multinational KEYNOTE-826 phase III clinical trial included 617 patients with persistent, recurrent, or metastatic cervical cancer who were not already treated with systemic chemotherapy and were not eligible for curative treatment with surgery or radiation therapy.
Prior treatment with radiosensitizing chemotherapy was allowed.
Patients were randomly assigned to receive either pembrolizumab with chemotherapy, with or without bevacizumab (308 participants), or placebo with chemotherapy, with or without bevacizumab (309 participants), for up to 35 cycles.
Of the participants, 88.8% had a PD-L1 combined positive score of 1 or higher and 51.4% had a PD-L1 combined positive score of 10 or higher.
The dual primary endpoints of the study were OS and PFS.
Researchers are hoping to further understand the role of pembrolizumab in locally advanced cervical cancer, which is being studied in a separate, ongoing phase III clinical trial.