The European Commission has approved cemiplimab-rwlc monotherapy for the treatment of adult patients with recurrent or metastatic cervical cancer who have progressed on or after platinum-based chemotherapy.
The European Commission has approved cemiplimab-rwlc (Libtayo) monotherapy for the treatment of adult patients with recurrent or metastatic cervical cancer who have progressed on or after platinum-based chemotherapy.1
The approval was based on findings from the phase 3 EMPOWER-Cervical 1 trial (NCT03257267). Cemiplimab induced a 31% reduction in the risk of death in the overall population (HR, 0.69; 95% CI, 0.56-0.84; 2-sided P <.001) and 27% in the squamous cell carcinoma (SCC) population (HR, 0.73; 95% CI, 0.58-0.91; 1-sided P = .003) vs investigator’s choice of chemotherapy.2
“Despite recent advancements in the prevention and treatment of cervical cancer, there remain limited options for people with recurrent or metastatic cases,” Israel Lowy, MD, PhD, senior vice president, Translational and Clinical Sciences, Oncology, at Regeneron, stated in a press release. “[Cemiplimab] was the first PD-1 inhibitor to demonstrate significant improvements in survival compared to chemotherapy in a phase 3 trial. With this fourth approval from the European Commission, [cemiplimab] can now be extended to appropriate patients in the European Union with advanced cervical cancer, irrespective of their PD-L1 status or histology."
The open-label, multicenter EMPOWER-Cervical 1 trial evaluated cemiplimab monotherapy vs investigator’s choice of chemotherapy in patients at least 18 years of age with recurrent or metastatic cervical cancer who had progressed on platinum-based chemotherapy. Acceptable histologies included squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma.3
Patients were allowed to enroll regardless of PD-L1 expression. Other inclusion criteria included an ECOG performance status of 0 or 1 and adequate organ function. Patients were also required to have prior treatment with bevacizumab (Avastin) unless there was a clinically documented reason why it was not administered.
Key exclusion criteria included ongoing or recent evidence of significant autoimmune disease, prior treatment with an anti–PD-1/PD-L1 agent, prior treatment with other systemic immune-modulating agents within 28 days of randomization, or active/untreated brain metastases.
Patients were randomly assigned to receive 350 mg of cemiplimab every three weeks (n = 304) or pemetrexed, vinorelbine, topotecan, irinotecan, or gemcitabine (n = 304).
The primary end point was overall survival (OS), which was analyzed first in patients with SCC, then in the overall population. Key secondary end points consisted of progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety.
The median patient age was 51 years (range, 22-87). Notably, 77.8% of patients had SCC and 22.2% had adenocarcinoma or adenosquamous carcinoma.
The trial was stopped early in March 2021 at the second planned interim analysis. The independent data monitoring committee made a unanimous recommendation based on the OS benefit observed with cemiplimab in patients with SCC.
Additional data showed that in the overall population, cemiplimab elicited a median OS of 12.0 months (95% CI, 10.3-13.5) compared with 8.5 months (95% CI, 7.5-9.6) with chemotherapy. In the SCC population, the median OS was 11.1 months (95% CI, 9.2-13.4) with cemiplimab vs 8.8 months (95% CI, 7.6-9.8) with chemotherapy.
In the overall population, those treated with cemiplimab achieved a median PFS of 2.8 months (95% CI, 2.6-3.9) vs 2.9 months (95% CI, 2.7-3.4) for those treated with chemotherapy (HR, 0.75; 95% CI, 0.63-0.89; 2-sided P <.001). In the SCC population, the median PFS was 2.8 months (95% CI, 2.6-4.0) with cemiplimab vs 2.9 months (95% CI, 2.7-3.9) with chemotherapy (HR, 0.71; 95% CI, 0.58-0.86; two-sided P < .001).
In the overall population, cemiplimab produced an ORR of 16.4% (95% CI, 12.5%-21.1%) compared with 6.3% (95% CI, 3.8%-9.6%) for chemotherapy (2-sided P <.001). The estimated median DOR in the overall patient population was 16.4 months (95% CI, 12.4–not reached) with cemiplimab vs 6.9 months (95% CI, 5.1-7.7) with chemotherapy. In the SCC population, the ORR was 17.6% (95% CI, 13.0%-23.0%) with cemiplimab compared with 6.7% (95% CI, 3.9%-10.7%) for chemotherapy (2-sided P <.001).
Investigators observed no new safety signals were observed with cemiplimab. Adverse effects (AEs) were reported in 88.3% of the patients who received cemiplimab vs 91.4% of those administered chemotherapy; grade 3 or higher AEs occurred in 45.0% and 53.4% of patients in the cemiplimab and chemotherapy arms, respectively.
Grade 3 or higher AEs that occurred more frequently in the cemiplimab arm compared with the chemotherapy arm included urinary tract infection (5.0% and 2.8% in the cemiplimab arm and chemotherapy arm, respectively), back pain (1.3% and 0.7%), asthenia (2.3% and 1.0%), arthralgia (0.3% and 0%) and pyrexia (0.3% and 0%).
“Consistent with our mission to bring the best treatments to patients across Europe living with gynecological cancers, we are proud to have been a part of the landmark [EMPOWER Cervical-1] trial for [cemiplimab],” Ignace Vergote, MD, PhD, investigator and gynecologist oncologist at University Hospitals Leuven in Belgium, and vice-chair of the Trial Steering Committee, said in a news release.
“[Cemiplimab] is an important advancement for patients with recurrent or metastatic cervical cancer whose disease has progressed following platinum-based chemotherapy and could offer a new standard of care in this setting. We are grateful to those who participated in the trial and to our partners at Regeneron, ENGOT, the GOG Foundation and NRG Oncology-Japan without whom this approval would not have been possible.”