Cemiplimab Reduces Risk of Death by 31% Vs Chemotherapy in Advanced Cervical Cancer

Krishnansu S. Tewari, MD

The PD-1 inhibitor cemiplimab (Libtayo) resulted in a 31% reduction in the risk of death compared with chemotherapy in patients with recurrent or metastatic cervical cancer who have progressed on chemotherapy, according to data from a phase 3 trial presented as part of the ESMO Virtual Plenary.

In the overall patient population, the patients who received treatment with cemiplimab (n = 304) experienced a significant improvement in overall survival (OS) vs chemotherapy (HR, 0.69; 95% CI, 0.56-0.84; P = .00011). Cemiplimab also resulted in a 25% reduction in the risk of disease progression (HR, 0.75; 95% CI, 0.63-0.89; P = .00048).

Moreover, the PD-1 inhibitor elicited an objective response rate (ORR) of 16% (n = 50) vs just 6% (n = 19) with chemotherapy (95% CI, 13%-21%; P = .00004). Per Kaplan Meier estimates, the median duration of response in the investigative arm was 16 months (95% CI, 12–not evaluable) vs 7 months (95% CI, 5-8) in the control arm.

“In this phase 3 trial, [cemiplimab] demonstrated a significant improvement in OS in women with advanced cervical cancer after progression on chemotherapy, reducing the risk of death by 31% compared to chemotherapy in the overall population,” trial investigator Krishnansu S. Tewari, MD, who is also the professor and director of the Division of Gynecologic Oncology at the University of California, Irvine, stated in a press release. “Improvements in progression-free survival [PFS] and ORR were also demonstrated in the overall population compared to chemotherapy.”

In the open-label, multicenter trial, investigators examined single-agent cemiplimab vs investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer that had progressed on platinum-based chemotherapy. Seventy-eight percent of participants had squamous cell carcinoma, while 22% had adenocarcinoma or adenosquamous carcinoma.

The median age of study participants was 51 years. Patients were randomized to receive either cemiplimab monotherapy at a dose of 350 mg every 3 weeks, or investigator’s choice of chemotherapy in the form of either pemetrexed, vinorelbine, topotecan, irinotecan, or gemcitabine. The primary end point of the trial was OS, assessed first in patients with squamous cell carcinoma and then in the total study population.

In March 2021, the trial was stopped early due to the highly significant OS benefit observed with cemiplimab in patients with squamous cell disease, after a unanimous recommendation from the independent data monitoring committee.

Additional data from the trial showed that among those with squamous cell carcinoma, cemiplimab (n = 239) also resulted in significant benefit compared with chemotherapy (n = 238). In this subset, the PD-1 inhibitor resulted in a 27% reduction in the risk of death (HR, 0.73; 95% CI, 0.58-0.91; P = .00306) and a 29% reduction in the risk of disease progression (HR, 0.71; 95% CI, 0.58-0.86; P = .00026). Moreover, cemiplimab induced an ORR of 18% (n = 49; 95% CI, 13%-23%) in this population vs 7% (n = 16; 95% CI, 4%-11%) with chemotherapy.

Results from a post-hoc analysis examining cemiplimab (n = 65) vs chemotherapy (n = 66) specifically in patients with adenocarcinoma showed that the immunotherapy led to a 44% reduction in the risk of death (HR, 0.56; 95% CI, 0.36-0.85; P <.005) and a 9% reduction in the risk of disease progression (HR, 0.91; 95% CI, 0.62-1.34). Here, cemiplimab elicited an ORR of 12% (n = 8; 95% CI, 6%-23%) vs 5% (n = 3; 95% CI, 1%-13%) with chemotherapy.

Regarding safety, no new signals were observed with cemiplimab. Results from a safety evaluation, which was done in 300 patients who received cemiplimab and 290 patients who were given chemotherapy. Toxicities were reported in 88% and 91% of those in the investigative and control arms, respectively.

The most frequently experienced adverse effects (AEs) in the cemiplimab and chemotherapy arms, respectively, were anemia (25% vs 45%), nausea (18% vs 33%), fatigue (17% vs 16%), vomiting (16% vs 23%), decreased appetite (15% vs 16%), and constipation (15% vs 20%).

AEs that were grade 3 or higher in severity were reported in 45% of those given cemiplimab vs 53% of those who received chemotherapy. The most common grade 3 or higher AEs reported in the investigative and control arms, respectively, were asthenia (2% vs 1%) and pyrexia (less than 1% vs 0%).

Immune-related toxicities were experienced by 16% and less than 1% of those in the cemiplimab and chemotherapy arms, respectively; 6% and less than 1% of these patients experienced an immune-related AE that was grade 3 or higher.

Eight percent of patients who received cemiplimab discontinued treatment due to toxicities compared with 5% of those who were given chemotherapy.

“Taken together, this landmark trial—which enrolled patients regardless of PD-L1 expression status—helps support the use of [cemiplimab] as a potential new second-line treatment for women with advanced cervical cancer who face a poor prognosis and limited treatment options,” Tewari added in the release.

Reference

1. Positive phase 3 Libtayo (cemiplimab) results in advanced cervical cancer presented at ESMO Virtual Plenary. News release. Sanofi. May 12, 2021. Accessed May 13, 2021. https://bit.ly/3fe9cxm