Adding the PD-1 inhibitor pembrolizumab to chemotherapy, with or without bevacizumab, improved overall survival and progression-free survival in patients with persistent, recurrent, or metastatic cervical cancer, regardless of whether the cancer expressed PD-L1. These findings from the KEYNOTE-826 trial will be presented by Bradley J. Monk, MD, FACS, FACOG, and colleagues at the 2023 ASCO Annual Meeting (Abstract 5500).
Bradley J. Monk, MD, FACS, FACOG
The multinational phase III KEYNOTE-826 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 (n = 308) or placebo with chemotherapy with or without bevacizumab (n = 309) for up to 35 cycles. Of the participants, 88.8% had a PD-L1 combined positive score (CPS) of 1 or higher and 51.4% had a PD-L1 CPS of 10 or higher. The dual primary endpoints of the study were overall survival and progression-free survival.
Overall and Progression-Free Survival Results
At a median follow-up of 39.1 months, the combination of pembrolizumab with chemotherapy improved both overall survival and progression-free survival in all trial participants, regardless of PD-L1 expression and whether bevacizumab was received. These long-term follow-up results support earlier findings from the study.
Overall survival was 28.6 months in the pembrolizumab group vs 16.5 months in the placebo group for those with a PD-L1 CPS of 1 or higher, 29.6 months vs 17.4 months for those with a PD-L1 CPS of 10 or higher, and 26.4 months vs 16.8 months for all participants. Progression-free survival 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 CPS of 1 or higher, by 42% in patients with a PD-L1 CPS 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 anemia (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 Dr. Monk, Professor in the Division of Gynecologic Oncology at Creighton University School of Medicine, HonorHealth Research Institute in Phoenix. “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.”
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.
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.
Merry Jennifer Markham, MD, FACP, FASCO
“The results of this study solidify the addition of pembrolizumab to chemotherapy with or without bevacizumab in people with persistent, recurrent, or metastatic cervical cancer as the front-line standard of care for this disease. Survival significantly improved with this approach, regardless of PD-L1 expression, further supporting its use for all patients in this population,” said ASCO Expert Merry Jennifer Markham, MD, FACP, FASCO.
Disclosure: The study was funded by Merck & Co., Inc. For full disclosures of the study authors, visit coi.asco.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.