Boosting the Maternal Microbiome Sharply Reduces Biliary Atresia in Early-Stage Study
January 21, 2022 03:00pm
By Ashley Gallagher, Assistant Editor
A phase 3 trial investigating the PD-1 inhibitor cemiplimab in patients with recurrent or metastatic cervical cancer who had previously progressed on chemotherapy showed a significant improvement in overall survival.
A phase 3 trial investigating the PD-1 inhibitor cemiplimab (Libtayo, Regeneron) in patients with recurrent or metastatic cervical cancer who had previously progressed on chemotherapy showed a significant improvement in overall survival (OS), with a reduction in the risk of death by 31% compared to chemotherapy in the overall population, according to a presentation at the European Society for Medical Oncology Virtual Plenary.
These positive results add to the previously reported data showing an improvement in OS with cemiplimab compared to chemotherapy. In light of these positive findings, the data from this trial will be used as the basis for regulatory submissions in 2021.
"Improvements in progression-free survival [PFS] and objective response rate [ORR] 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 [cemiplimab] as a potential new second-line treatment for women with advanced cervical cancer who face a poor prognosis and limited treatment options," said trial investigator Krishnansu S. Tewari, MD, professor and director of the Division of Gynecologic Oncology at the University of California, Irvine, in a press release.
Currently, cervical cancer is the fourth leading cause of cancer mortality in women globally, with the most frequently diagnosed age group being women aged 35 to 44 years. Every year, approximately 570,000 women are diagnosed with cervical cancer, with deaths among those diagnosed totaling more than 250,000 annually. In the United States alone, there are approximately 14,500 patients diagnosed annually, with approximately 4000 women dying from the disease each year.
Although human papillomavirus infection is the cause of a majority of cases, approximately 80% are also classified as squamous cell carcinoma (SCC), which occurs from within cells in the lining at the bottom of the cervix. The remaining 20% of cases are classified as adenocarcinomas, which arises from glandular cells in the upper cervix. When detected early, cervical cancer is generally curable and can be managed; however, in advanced stages, the treatment options available become limited.
In the overall patient population, the investigators found that OS, PFS, and ORR significantly improved for those treated with cemiplimab (n=304), compared to chemotherapy (n=304). Specifically, the investigators observed a 31% reduction in mortality risk (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.56-0.84; one-sided p=0.00011), a 25% reduction in disease progression risk (HR: 0.75; 95% CI: 0.63-0.89; one-sided p=0.00048), and 16% ORR (50 patients; 95% CI: 13-21%; one-sided p=0.00004), compared to 6% with chemotherapy (19 patients).
Among this population, the median duration of response was 16 months with cemiplimab (95% CI: 12 months to not yet evaluable) and 7 months with chemotherapy (95% CI: 5-8 months), per Kaplan-Meier estimates.
Seventy-eight percent of trial participants were found to have advanced cervical cancer classified as SCC and also went on to experience significant improvements following treatment with cemiplimab (n=239) versus chemotherapy (n=238).
Specifically, patients in this population experienced a 27% reduction in mortality risk (HR: 0.73; 95% CI: 0.58-0.91; one-sided p=0.00306), a 29% reduction in disease progression risk (HR: 0.71; 95% CI: 0.58-0.86; one-sided p=0.00026), and 18% ORR (42 patients; 95% CI: 13-23%) compared to 7% with chemotherapy (16 patients; 95% CI: 4-11%).
Although the investigators did not set the assessment of adenocarcinoma as a pre-specified endpoint, a post-hoc analysis demonstrated that patients treated with cemiplimab (n=65) compared to chemotherapy (n=66) experienced a 44% reduction in mortality risk (HR: 0.56; 95% CI: 0.36-0.85; nominal one-sided p<0.005), a 9% reduction in disease progression risk (HR: 0.91; 95% CI: 0.62-1.34), and 12% ORR (8 patients; 95% CI: 6-23%), compared to 5% with chemotherapy (3 patients; 95% CI: 1-13%).
Additionally, the phase 3 trial demonstrated that patients treated with cemiplimab experienced an improvement or maintenance of their baseline Global Health Status/Quality of Life (GHS/QOL) over time. However, patients treated with chemotherapy experienced a deterioration that was clinically significant by cycle 8, per the European Organisation for Research and Treatment of Cancer QLQ-C30 (overall estimated mean change [95% CI]: improvement of 1.01 [-2.033, 4.047] for Libtayo, worsening of -6.81 [-10.977, -2.637] for chemotherapy; difference: 7.81; one-sided nominal p=0.00040).
The investigators observed no safety signals for patients treated with cemiplimab. The investigators had assessed safety in patients who received at least 1 dose of study treatment, which included 300 patients in the cemiplimab group (median duration of exposure: 15 weeks; range: 1-101 weeks) and 290 patients in the chemotherapy group (median duration of exposure: 10 weeks; range: 1-82 weeks).
In terms of adverse events (AEs) observed during the trial, investigators found 88% of cemiplimab patients and 91% of chemotherapy patients experienced AEs. In 15% or more of cemiplimab patients, AEs included anemia (25% cemiplimab, 45% chemotherapy), nausea (18% cemiplimab, 33% chemotherapy), fatigue (17% cemiplimab, 16% chemotherapy), vomiting (16% cemiplimab, 23% chemotherapy), decreased appetite (15% cemiplimab, 16% chemotherapy), and constipation (15% cemiplimab, 20% chemotherapy).
Additionally, grade 3 or higher AEs were observed in 45% of cemiplimab patients and 53% of chemotherapy patients, whereas in 15% or more of patients, certain grade 3 or higher AEs were observed more frequently in the cemiplimab group. These AEs included asthenia (2% cemiplimab, 1% chemotherapy) and pyrexia (less than 1% cemiplimab, 0% chemotherapy).
The investigators also observed immune-related AEs in 16% of cemiplimab patients and fewer than 1% of chemotherapy patients. The AEs at grade 3 or higher occurred in 6% of cemiplimab patients and fewer than 1% of chemotherapy patients. However, patients discontinuing treatment due to AEs only occurred among 8% of cemiplimab patients and 5% of chemotherapy patients.
Positive Phase 3 Libtayo® (cemiplimab) Results in Advanced Cervical Cancer Presented at ESMO Virtual Plenary. Tarrytown, NY: Regeneron Pharmaceuticals; May 12, 2021. https://investor.regeneron.com/news-releases/news-release-details/positive-phase-3-libtayor-cemiplimab-results-advanced-cervical. Accessed May 17, 2021.