Addition of the PD-1 inhibitor pembrolizumab to chemotherapy patients with persistent, recurrent, or metastatic cervical cancer with or without bevacizumab, regardless of whether the cancer expresses PD-L1 improved overall survival and progression-free survival. These results from the KEYNOTE-826 trial Bradley J. Monk, MD, FACS, FACOGand colleagues at the 2023 ASCO Annual Meeting (Abstract 5500).
Bradley J. Monk, MD, FACS, FACOG
About KEYNOTE-826
The multinational phase III KEYNOTE-826 clinical trial included patients with persistent, recurrent, or metastatic cervix not previously treated with systemic chemotherapy and not eligible for curative treatment with surgery or radiation therapy. 617 cancer patients participated. Prior treatment with radiosensitizing chemotherapy was allowed.
Patients were randomized to receive up to 35 cycles of chemotherapy with or without pembrolizumab and bevacizumab (n = 308) or placebo with or without bevacizumab (n = 309). rice field. Of the participants, 88.8% had a PD-L1 Total Positive Score (CPS) of 1 or higher, and 51.4% had a PD-L1 CPS of 10 or higher. Her two primary endpoints for this study were overall survival and progression-free survival.
Overall and Progression-Free Survival Outcomes
At a median follow-up of 39.1 months, the combination of pembrolizumab and chemotherapy improved both overall survival and progression-free survival in all study participants, regardless of PD-L1 expression and bevacizumab treatment. These long-term follow-up results support the early findings of the study.
Overall survival was 28.6 months with pembrolizumab in patients with PD-L1 CPS ≥1 vs. 16.5 months in placebo group, and 29.6, 17.4 and 26.4 months in patients with PD-L1 CPS ≥10 was. For all participants, he was 16.8 months old. Progression-free survival for all participants was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group. The combination of pembrolizumab and chemotherapy reduced the risk of death by 40% in patients with PD-L1 CPS ≥1, 42% in patients with PD-L1 CPS ≥10, and 37% in all patients. .
Adverse events of grade 3 or higher were more common in the pembrolizumab group, with 82.4% of participants experiencing an event compared with 75.4% in the placebo group. The most common grade ≥3 side effects in pembrolizumab and placebo groups were anemia (30.3% vs. 27.8%), neutropenia (12.4% vs. 9.7%), and hypertension (10.4% vs. 11.7%) .
“Prior to KEYNOTE-826, the standard of care for people with this diagnosis was platinum-based paclitaxel chemotherapy in combination with bevacizumab treatment,” said lead author Dr. Monk, professor of gynecologic oncology at the Creighton University School of Medicine. . , his HonorHealth Institute in Phoenix. “This study demonstrates that early administration of immunotherapy confers a substantial overall survival benefit compared to second-line therapy. We have demonstrated survival benefits for pembrolizumab, providing a treatment option for this patient population with high unmet need.”
next step
Pembrolizumab is now approved by the U.S. Food and Drug Administration for the treatment of PD-L1-expressing persistent, recurrent or metastatic cervical cancer in combination with chemotherapy, with or without bevacizumab It has been. The study suggests that the addition of pembrolizumab to chemotherapy may be an effective first-line treatment option for people with this diagnosis, regardless of whether their cancer expresses PD-L1. indicates that there is
The researchers hope to better understand the role of pembrolizumab in locally advanced cervical cancer, which is being studied in another ongoing phase III clinical trial.
ASCO Perspective
Mary Jennifer Markham, MD, FACP, FASCO
“The results of this study firmly establish the addition of pembrolizumab to chemotherapy with or without bevacizumab for patients with persistent, recurrent, or metastatic cervical cancer as the frontline standard of care for this disease. Regardless of PD-L1 expression, this approach significantly improved survival, further supporting the use of this approach for all patients in this population,” said the ASCO expert. Mary Jennifer Markham, MD, FACP, FASCO.
Disclosure: For full disclosure of study authors, please visit: coi.asco.org.
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