Overall survival (OS) was significantly improved with cemiplimab as compared to investigator’s choice of chemotherapy in patients with recurrent/metastatic cervical cancer and progression after first-line platinum-based treatment, according to interim findings from a phase III study presented at the ESMO Virtual Plenaries (12 & 13 May 2021).
Krishnansu Sujata Tewari of the Obstetrics & Gynaecology Department, UC Irvine Medical Centre in Orange, CA, USA presented interim results on behalf of co-investigators from the open-label, randomised, multicentre, phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study (NCT03257267). He explained that salvage chemotherapy has been shown to be ineffective in patients with recurrent/metastatic cervical cancer following progression on first-line platinum-based chemotherapy with or without bevacizumab, thus prompting this evaluation of the anti-PD1 agent cemiplimab.
The study compared cemiplimab with investigator’s choice of single agent chemotherapy in patients with recurrent/metastatic cervical cancer that progressed after first-line platinum-based treatment.
Enrollment was regardless of PD-L1 expression. Following 1:1 randomisation 304 patients were treated with cemiplimab at 350 mg per i.v. every 3 weeks and 304 received investigator’s choice of chemotherapy comprised of either pemetrexed, vinorelbine, gemcitabine, irinotecan, or topotecan for up to 96 weeks. The patients were stratified by histology (squamous cell carcinoma [SCC; n=477] / adenocarcinoma or adenosquamous [AC; n=131]). The patients’ median age was 51 years (range, 22 to 87) and the ECOG performance score 0 in 46.5% and 1 in 53.5% of patients.
The primary endpoint was OS, which was analysed hierarchically in patients with SCC followed by the total population of patients. Progression-free survival (PFS), objective response rate (ORR), quality of life (QoL) and safety served as additional endpoints. The interim analysis was scheduled when 85% events had occurred among patients with SCC.
The median exposure to cemiplimab was 15 weeks (range, 1.4 to 100.7).
Statistically significant OS improvements were observed across both histologies and in the overall population
The interim analysis demonstrated that all endpoints evaluated favoured cemiplimab in the overall and SCC patient population, including OS, PFS, ORR, and mean change in QoL from baseline in the SCC patients.
Regarding the primary endpoint, median OS in the total population was 12.0 months with cemiplimab compared to 8.5 months with chemotherapy (hazard ratio [HR] 0.69;
95% confidence interval [CI] 0.56‒0.84; p < 0.001).
Among 239 SCC patients on cemplimab, median OS was 11.1 months compared to 8.8 months in 238 SCC patients receiving chemotherapy (HR 0.73; 95% CI 0.58‒0.91; p = 0.003).
In the AC population, the 65 patients receiving cemplimab demonstrated median OS of 13.3 months compared to 7.0 months in the 66 patients receiving chemotherapy (HR 0.56; 95% CI 0.36‒0.85; p < 0.005 nominal p value, not adjusted for multiplicity).
Treatment emergent adverse events (TEAEs) were lower with cemplimab versus chemotherapy; the most commonly reported TEAEs of any grade were anaemia (25% versus 45%), nausea (18% versus 33%), and vomiting (16% versus 23%), respectively.
Eight percent of patients treated with cemplimab discontinued due to AEs versus 5% of patients on investigator’s choice of chemotherapy.
Based on these interim findings, the authors were able to conclude that cemiplimab significantly improves OS over single agent chemotherapy in patients with recurrent/metastatic cervical cancer with progression following first-line platinum-based therapy. Furthermore, cemiplimab activity was regardless of PD-L1 status or histology. According to the authors, no new safety signals were observed.
The study was funded by Regeneron Pharmaceuticals, Inc. and Sanofi.
Tewari KS, Monk BJ, Vergote I, et al. EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9: Interim analysis of phase 3 trial of cemiplimab vs investigator’s choice (IC) chemotherapy (chemo) in recurrent/metastatic /R/M) cervical carcinoma. ESMO Virtual Plenaries (12 & 13 May 2021).