FDA Grants Priority Review to Cemiplimab for Advanced Cervical Cancer

The FDA has granted cemiplimab-rwlc a priority review based on findings from the largest to-date, randomized clinical trial in advanced cervical cancer.

The FDA has granted priority review to cemiplimab-rwlc (Libtayo) in response to the supplemental biologics license application (sBLA) on the indication of recurrent or metastatic cervical cancer whose disease progressed on or after chemotherapy.1

The priority review is based off findings from the open-label, multi-center phase 3 EMPOWER-Cervical 1 trial, which is the largest randomized clinical trial in advanced cervical cancer to-date. Updated findings presented at the 2021 ESMO Virtual Plenary revealed that cemiplimab demonstrated superior overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), compared with chemotherapy, as an advanced cervical cancer therapy. 2

The FDA set a target action date of January 30, 2022.

Overall, the 304 participants treated with cemiplimab–a fully human monoclonal antibody that functions by targeting the PD-L1 immune checkpoint receptor on T-cells–experienced a 31% reduced risk of mortality (HR, 0.69; 95% CI, 0.56-0.84; P = .00011), a 25% reduced risk of disease progression (HR, 0.75; 95% CI, 0.63 -0.89; P = .00048), and an ORR of 16% compared with 6% with chemotherapy (95% CI, 13%-21%; P = .00004).

"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," said trial investigator Krishnansu S. Tewari, MD, professor and director of the Division of Gynecologic Oncology at the University of California, Irvine. "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."

The study assessed women with recurrent or metastatic cervical cancer whose disease had progressed beyond platinum-based chemotherapy. PD-L1 expression status was not a factor in participant eligibility. Women from 14 countries participated in the trial, including the U.S., Japan, Taiwan, South Korea, Canada, Russia, Poland, Spain, Brazil, Australia, the UK, Italy, Greece and Belgium. Seventy-eight percent of patients had squamous cell carcinoma (SCC) and 22% had adenosquamous carcinoma.

In addition, a smaller subset of patients in the trial whose disease was identified as SCC experienced positive results with cemiplimab compared with chemotherapy. These 238 patients experienced a 27% reduced risk of mortality (HR, 0.73; 95% CI, 0.58-0.91; P = .00306), a 29% reduced risk of disease progression (HR, 0.71; 95% CI, 0.58 -0.86; P = .00026), and an ORR of 18% compared with 7% with chemotherapy (95% CI, 13%-23%).

A post-hoc analysis also determined that the 65 patients with adenocarcinoma experienced a 44% reduced risk of mortality (HR, 0.56; 95% CI, 0.36-0.85; P < .005), a 9% reduced risk of disease progression (HR, 0.91; 95% CI, 0.62-1.34), and an ORR of 12% compared with 5% with chemotherapy (95% CI, 1%-13%).

Notably, findings also determined that patients treated with the novel regimen experienced a superior global health status/quality of life (GHS/QoL) than those treated with chemotherapy. The change in status became clinically meaningful starting at cycle 8, with the improvement with cemiplimab being 1.01 and the worsening for chemotherapy being -6.81 (95% CI).

Investigators reported no new safety signals. Adverse events (AEs) occurred in 88% of participants in the experimental arm and 91% of the control arm. Common AEs included anemia (25% vs 45%, respectively), nausea (18% vs 33%), fatigue (17% vs 16%), vomiting, (16% vs 23%), decreased appetite (18% vs 33%), and constipation (15% vs 20%).

AEs with a grade 3 or higher severity occurred in 45% of patients receiving cemiplimab and 53% of patients receiving chemotherapy. These AEs included asthenia (2% vs 1%, respectively), and pyrexia (less than 1% vs 0%). In addition, immune-related were observed in 16% of patients receiving cemiplimab and in less than 1% of patients on chemotherapy.

Discontinuations were necessary among 8% of patients in the experimental cohort and in 5% of the control cohort.

Providers should ask their patients about any immune-related problems, organ transplant history, allogeneic stem cell transplant history, or nervous system conditions, before prescribing cemiplimab, as those factors may influence the suitability of the drug.