Clinical trial EMPOWER-Cervical 1 demonstrates an overall survival benefit of using cemiplimab as monotherapy, compared with chemotherapy of investigator’s choice, for patients with recurrent or metastatic cervical cancer who have progressed to first-line chemotherapy.
Despite already validated screening programs for cervical cancer using cytological assessments, high-risk human papillomavirus (HPV) DNA detection, and the availability of effective prophylactic vaccines, approximately 600,000 new cases and 350,000 cervical cancer deaths occur worldwide each year.
Early invasive disease (International Federation of Gynecology and Obstetrics [FIGO] stage IB1 or IB2) is usually treated with radical hysterectomy and lymphadenectomy with or without adjuvant therapy. Patients with locally advanced carcinoma (FIGO stage IB3-IVA) receive chemoradiotherapy and high-dose intracavitary brachytherapy. Patients with persistent or recurrent disease after radiotherapy that is not amenable to curative pelvic exenteration with urinary diversion, as well as those with metastases (FIGO stage IVB), are treated with platinum-based chemotherapy, with or without bevacizumab.
Despite the improvement in overall survival conferred by antiangiogenic therapy, most patients experience progression after first-line platinum-containing therapy and have limited treatment options. In this sense, cemiplimab (anti PD-1), already approved to treat advanced non-melanoma skin cancer (Squamous Cell Carcinoma and Basal Cell Carcinoma), demonstrated clinical activity in this population.
EMPOWER-Cervical 1/GOG-3016/ENGOT-cx is a randomized, multicenter, phase 3 study that enrolled patients with recurrent or metastatic cervical cancer who had disease progression after first-line platinum-containing chemotherapy, regardless of their PD-L1 status. Patients were randomized (1:1) to receive cemiplimab (350 mg every 3 weeks) or investigator’s choice of single-agent chemotherapy. The primary endpoint was overall survival, progression-free survival and safety were also evaluated.
A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was higher in the cemiplimab group compared to the chemotherapy group (12.0 months vs. 8.5 months; HR 0.69; 95% CI, 0.56 to 0.84; two-sided P < 0.001). The overall survival benefit was consistent across both histologic subgroups (squamous cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also higher in the cemiplimab group compared with the chemotherapy group in the overall population (HR 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) of patients in the chemotherapy group. Objective response occurred in 18% (95% CI, 11 to 28) of patients treated with cemiplimab with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of patients who received cemiplimab and in 53.4% of those who received chemotherapy.
Cemiplimab treatment led to significantly longer overall survival than chemotherapy among patients with recurrent cervical cancer who had disease progression after first-line platinum-containing chemotherapy. Compared with the investigator’s choice of chemotherapy, treatment with cemiplimab resulted in 31% reduced risk of death in the overall population and 27% lower risk of death in the squamous cell carcinoma population.
Krishnansu S. Tewari, M.D. et al., Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med 2022; 386:544-555. DOI: 10.1056/NEJMoa2112187