As reported in The New England Journal of Medicine by Krishnansu S. Tewari, MD, and colleagues, the phase III EMPOWER-Cervical1/GOG-3016/ENGOT-cx9 trial has shown improved overall survival with cemiplimab-rwlc vs investigator’s choice of single-agent chemotherapy in patients with cervical cancer recurring after first-line platinum-based chemotherapy.
Krishnansu S. Tewari, MD
Study Details
In the international open-label trial, 608 women were randomly assigned between July 2017 and August 2020 (irrespective of PD-L1 status) to receive cemiplimab at 350 mg every 3 weeks for up to 96 weeks (n = 304) or investigator’s choice of single-agent chemotherapy selected prior to random assignment (n = 304). Chemotherapy options included pemetrexed at 500 mg/m2 every 21 days, topotecan at 1 mg/m2 daily for 5 days or irinotecan at 100 mg/m2 weekly for 4 weeks, gemcitabine at 1,000 mg/m2 on days 1 and 8 every 21 days, and vinorelbine at 30 mg/m2 on days 1 and 8 every 21 days. Overall, 78% of patients had squamous cell carcinoma and 22% had adenocarcinoma or adenosquamous carcinoma.
The primary endpoint was overall survival.
Overall Survival
The trial was stopped on the basis of prespecified criteria for efficacy squamous cell carcinoma population at the second planned interim analysis (at a median follow-up of 16.8 months).
Median duration of follow-up in the total population was 18.2 months (range = 6.0–38.2 months) at data cutoff in January 2021. In the total population, median overall survival was 12.0 months (95% confidence interval [CI] = 10.3–13.5 months) in the cemiplimab group vs 8.5 months (95% CI = 7.5–9.6 months) in the chemotherapy group (hazard ratio [HR] = 0.69, 95% CI = 0.56–0.84, P< .001). Median overall survival ranged from 6.5 months with topotecan to 11.8 months with irinotecan.
Among patients with squamous cell carcinoma, median overall survival was 11.1 months (95% CI = 9.2–13.4 months) vs 8.8 months (95% CI = 7.6–9.8 months), with a hazard ratio of 0.73 (95% CI = 0.58–0.91, P = .006). Among patients with adenocarcinoma or adenosquamous carcinoma, median overall survival was 13.3 months (95% CI = 9.6–17.6 months) vs 7.0 months (95% CI = 5.1–9.7 months), with a hazard ratio of 0.56 (95% CI = 0.36–0.85).
Among all patients, median progression-free survival was 2.8 months (95% CI = 2.6–3.9 months) with cemiplimab vs 2.9 months (95% CI = 2.7–3.4 months) with chemotherapy (HR = 0.75, 95% CI = 0.63–0.89, P < .001). As noted by the investigators, “The benefit with respect to progression-free survival with cemiplimab was driven by durable separation of the curves after median progression-free survival was reached.”
In the overall population, objective response was observed in 16.4% (95% CI = 12.5%–21.1%) vs 6.3% (95% CI = 3.8%–9.6%) of patients. Among 126 patients in the cemiplimab group with known PD-L1 status, objective response occurred in 18% (95% CI = 11%–28%) of 82 with tumor cell PD-L1 expression ≥ 1% and in 11% (95% CI = 4%–25%) of 44 with PD-L1 expression < 1%.
KEY POINTS
- Cemiplimab significantly improved overall survival vs single-agent chemotherapy.
- Benefit was observed in both the squamous cell carcinoma population and the adenocarcinoma/adenosquamous carcinoma population.
Adverse Events
Grade ≥ 3 adverse events occurred in 45.0% of patients in the cemiplimab group and 53.4% of the chemotherapy group; the most common in the cemiplimab group were anemia (12.0%) and urinary tract infection (5.0%) and the most common the chemotherapy group were anemia (26.9%) and neutropenia (9.0%). Serious adverse events occurred in 29.7% vs 26.9%. Adverse events led to discontinuation of study treatment in 8.7% vs 5.2% of patients. Immune-related adverse events of any grade occurred in 15.7% vs 0.7%. Adverse events led to death in five patients (1.7%) in the cemiplimab group and two patients (0.7%) in the chemotherapy group. No deaths in the cemiplimab group were considered related to study treatment.
The investigators concluded, “Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. “
Dr. Tewari, of the Division of Gynecologic Oncology, University of California, Irvine, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Regeneron Pharmaceuticals and Sanofi. For full disclosures of the study authors, visit nejm.org.
