Phase 3 Trial of Cemiplimab Shows Promise in Advanced Cervical Cancer

Aislinn Antrim, Associate Editor

The trial found positive results in both the overall study population of patients with advanced cervical cancer as well as subgroups with squamous cell carcinoma and adenocarcinoma.

A phase 3 clinical trial of cemiplimab (Libtayo) in patients with advanced cervical cancer found improvements in overall survival (OS) among the overall patient population as well as subgroups with squamous cell carcinoma (SCC) and adenocarcinoma, according to a press release.

Cemiplimab is the first immunotherapy to demonstrate an improvement in OS among patients with advanced cervical cancer, as well as progression-free survival (PFS) and objective response rate (ORR) compared to chemotherapy alone. These findings will form the basis of regulatory submissions later in 2021, according to the press release.

“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, in the press release. “Improvements in progression-free survival and objective response rate were also demonstrated in the overall population compared to chemotherapy.”

The phase 3, open-label, multi-center trial is the largest randomized clinical trial in advanced cervical cancer. It is investigating cemiplimab monotherapy compared to an investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer that has progressed on platinum-based chemotherapy. Patients were enrolled regardless of programmed death ligand-1 (PD-L1) expression status, with 78% having SCC and 22% having adenocarcinoma or adenosquamous carcinoma.

In the overall study population, patients treated with cemiplimab saw significant improvements in OS, PFS, and ORR compared to chemotherapy alone. These improvements included a 31% reduction in the risk of death, a 25% reduction in the risk of disease progression, and a 16% ORR, compared to a 6% ORR in chemotherapy monotherapy.

In the subgroup of patients with SCC, the investigators also saw significant improvements, including a 27% reduction in the risk of death and a 29% reduction in the risk of disease progression. Furthermore, they found an 18% ORR compared to a 7% ORR with chemotherapy.

Although assessment of adenocarcinoma was not a pre-specified endpoint, a post-hoc analysis from positive outcomes in this subgroup, as well. These results included a 44% reduction in the risk of death, a 9% reduction in the risk of disease progression, and a 12% ORR, compared to a 5% ORR with chemotherapy.

Patients treated with cemiplimab were able to generally improve and maintain their baseline Global Health Status/Quality of Life score over time, whereas the press release said patients treated with chemotherapy alone experienced a deterioration that became clinically meaningful starting at cycle 8.

No new safety signals were observed, and adverse events (AEs) were recorded in 88% of cemiplimab-treated patients and 91% of chemotherapy-treated patients. AEs occurring in 15% or more of the cemiplimab-treated arm include anemia, nausea, fatigue, vomiting, decreased appetite, and constipation.

“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,” Tewari concluded in the press release.

REFERENCE

Positive Phase 3 Libtayo (cemiplimab) results in advanced cervical cancer presented at ESMO Virtual Plenary [news release]. Sanofi; May 12, 2021. https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-12-19-35-00-2228565. Accessed May 14, 2021.