Results presented at part of the European Society for Medical Oncology Virtual Plenary show positive results of a phase 3 trial comparing cemiplimab with chemotherapy for previously treated cervical cancer.
Results of the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial (NCT03257267) of cemiplimab (Libtayo) in patients with recurrent or metastatic cervical cancer following chemotherapy were reported as part of the European Society for Medical Oncology (ESMO) Virtual Plenary, showing that the PD-1 inhibitor resulted in a statistically significant benefit to overall survival (OS) versus investigator’s choice of chemotherapy.
These results add to existing data that were reported in March 2021, when Sanofi and Regeneron, the companies responsible for developing the experimental therapy, announced an early stop to the trial based on a reduction in the risk of disease progression or death (HR, 0.69; 95% CI, 0.56-0.84; P = .00011).
“In this phase 3 trial, Libtayo demonstrated a significant improvement in overall survival in women with advanced cervical cancer after progression on chemotherapy, reducing the risk of death by 31% compared to chemotherapy in the overall population,” Krishnansu S. Tewari, MD, professor and director of the Division of Gynecologic Oncology at the University of California, Irvine, and a trial investigator, said in a press release. “Improvements in progression-free survival and objective response rate were also demonstrated in the overall population compared to chemotherapy. Taken together, this landmark trial–which enrolled patients regardless of PD-L1 expression status–helps support the use of Libtayo as a potential new second-line treatment for women with advanced cervical cancer who face a poor prognosis and limited treatment options.”
Cemiplimab monotherapy was administered at a dose of 350 mg every 3 weeks versus investigator’s choice of either pemetrexed, vinorelbine, topotecan, irinotecan, or gemcitabine.
Patients treated with cemiplimab (n = 304) also had improved progression-free survival (PFS) and objective response rate (ORR) compared with those receiving chemotherapy (n = 304). In the overall population, there was a 25% reduction in the risk of disease progression or death with cemiplimab versus chemotherapy (HR, 0.75; 95% CI, 0.63-0.89; P = .00048). Corresponding ORRs in the groups were 16% and 6% (P = .00004), with median response durations of 16 months (95% CI, 12-not reached) and 7 months (95% CI, 5-6), respectively.
Patients were further broken down by histology, with 78% of treated patients presenting with squamous cell carcinoma. Those treated with cemiplimab (n = 239) experienced a 27% reduction in the risk of death (HR, 0.73; 95% CI, 0.58-0.91; one-sided P = .00306). PFS (HR, 0.71; 95% CI, 0.58-0.86; one-sided P = .00026) and ORR (18% vs 7%) were also improved with cemiplimab compared with chemotherapy.
In patients with adenocarcinoma, a post hoc analysis revealed a 44% reduction in the risk of death (HR, 0.56; 95% CI, 0.36-0.85; nominal one-sided P <0.005) and a 9% reduction in the risk of disease progression (HR, 0.91; 95% CI, 0.62-1.34) with cemiplimab (n = 65) versus chemotherapy (n = 66). The ORRs were 12% and 5%, respectively, however assessment for this histologic subgroup was not a prespecified end point.
Of note, Global Health Status/Quality of Life was generally improved or maintained with cemiplimab over time, whereas treatment with chemotherapy typically resulted in a deterioration starting at about cycle 8 (P = .0004).
No new safety signals were noted with cemiplimab. Any-grade adverse events (AEs) occurred in 88% of patients treated with the experimental regimen versus 91% in the control group. Grade 3 or greater AEs occurring at a higher rate with cemiplimab included asthenia (2% vs 1%) and pyrexia (<1% vs 0%). Immune-related AEs occurred in 16% of patients receiving immunotherapy and 1% of patients on chemotherapy, and included 6% and 1%, respectively, that were grade 3 or higher events. Treatment discontinuation due to AEs occurred in 8% of those receiving cemiplimab and 5% on chemotherapy.
These data will support the application for regulatory submission in 2021.
1. Positive Phase 3 Libtayo® (cemiplimab) Results in Advanced Cervical Cancer Presented at ESMO Virtual Plenary. News release. Regeneron Pharmaceuticals, Inc. and Sanofi. May 12, 2021. Accessed May 13, 2021. https://prn.to/3huFSWl
2. Phase 3 trial of Libtayo (cemiplimab) monotherapy in advanced cervical cancer stopped early for positive result on overall survival. News release. Sanofi and Regenergon. March 15, 2021. Accessed March 15, 2021. https://bit.ly/3tmLCnG