EMA Endorses Cemiplimab Approval in Advanced Cervical Cancer

Cervical Cancer

The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for cemiplimab-rwlc (Libtayo) monotherapy for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after platinum-based chemotherapy.¹

The positive opinion is based on findings from the phase 3 EMPOWER-Cervical 1 trial (NCT03257267), in which cemiplimab led to a 31% reduction in the risk of death in the overall population (HR, 0.69; 95% CI: 0.56-0.84; two-sided P < .001) and 27% in the squamous cell carcinoma (SCC) population (HR, 0.73; 95% CI: 0.58-0.91; one-sided P = .003) compared with investigator’s choice of chemotherapy.²

The European Commission is expected to make a final decision on the application in the coming months.

EMPOWER-Cervical 1 is an open-label, multicenter trial that investigated cemiplimab monotherapy vs investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer who had progressed on platinum-based chemotherapy. Patients were allowed to enroll regardless of PD-L1 expression.

Patients were randomly assigned to receive 350 mg of cemiplimab every three weeks (n = 304) or pemetrexed (Alimta), 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 total population. Progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety served as key secondary end points.

The median patient age was 51 years (range, 22-87); 77.8% of patients had SCC and 22.2% had adenocarcinoma or adenosquamous carcinoma. Approximately 40% of the patients in each arm had received at least 1 prior line of systemic therapy for recurrence, and approximately 50% in each arm had received prior bevacizumab (Avastin).

In March 2021 at the second planned interim analysis, the trial was stopped early following a unanimous recommendation by the Independent Data Monitoring Committee based on the OS benefit with cemiplimab in patients with SCC.

Additional results showed that in the overall population, the median OS with cemiplimab was 12.0 months (95% CI, 10.3-13.5) vs 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 with chemotherapy (95% CI, 7.6-9.8).

In the overall population, the median PFS was 2.8 months (95% CI, 2.6-3.9) with cemiplimab vs 2.9 months (95% CI, 2.7-3.4) with chemotherapy (HR, 0.75; 95% CI, 0.63-0.89; two-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, the ORR was 16.4% (95% CI, 12.5%-21.1%) with cemiplimab vs 6.3% (95% CI, 3.8%-9.6%) with chemotherapy (two-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%) vs 6.7% (95% CI, 3.9%-10.7%) in the cemiplimab and chemotherapy arms, respectively (two-sided P < .001).

Regarding safety, no new signals were observed with cemiplimab.

Adverse effects (AEs) occurred in 88.3% of the patients who received cemiplimab and in 91.4% of those who received chemotherapy; grade 3 or higher AEs occurred in 45.0% and 53.4% of patients, respectively.

Grade 3 or higher AEs that occurred more frequently with cemiplimab than chemotherapy, respectively, included urinary tract infection (5.0% vs 2.8%), back pain (1.3% vs 0.7%), asthenia (2.3% vs 1.0%), arthralgia (0.3% vs 0%) and pyrexia (0.3% vs 0%).

References

1. Libtayo (cemiplimab) receives positive CHMP opinion recommending approval to treat advanced cervical cancer. News release. Regeneron Pharmaceuticals. October 14, 2022. Accessed October 14, 2022. https://bit.ly/3rWsH4g
2. Tewari KS, Monk BJ, Vergote I, et al. Survival with cemiplimab in recurrent cervical cancer. N Engl J Med. 2022;386(6):544-555. doi:10.1056/NEJMoa2112187