Results from a phase 3 trial showing prolonged survival with the immunotherapy cemiplimab (Libtayo) in the second-line treatment of recurrent or metastatic cervical cancer are being hailed as “practice changing.”
The drug is not as yet approved for this indication, although the company has said that it will use these new data for regulatory submissions in 2021.
Cemiplimab was recently approved in the United States for use in certain patients with non–small cell lung cancer and for the treatment of basal cell carcinoma. It has been marketed since 2018 for use in the treatment of advanced cutaneous squamous cell carcinoma.
The new results in cervical cancer come from the second interim analysis of the randomized, open-label EMPOWER-CERVICAL 1/GOG-3016/ENGOT-CX9 study.
The trial’s independent data monitoring committee (IDMC) recommended that the trial be stopped early on the basis of efficacy.
The new results were presented on May 12 at a virtual plenary session of the annual meeting of the European Society of Medical Oncology, and they were published online May 12 in Annals of Oncology.
“In the largest randomized study conducted to date in this population, cemiplimab is the first immunotherapy to demonstrate a statistically significant and clinically meaningful survival benefit in recurrent or metastatic cervical carcinoma following progression after first-line platinum-containing chemotherapy,” commented first author Krishnansu S. Tewari, MD, a professor and director of the Division of Gynecologic Oncology, Obstetrics and Gynecology at the University of California, Irvine.
“Cemiplimab can provide a new standard of care treatment option for this population associated with a very poor prognosis,” he added.
Reacting to the presentation, discussant Mansoor Raza Mirza, MD, chief oncologist at Copenhagen University Hospital, Copenhagen, Denmark, said the new results are “impressive.”
“These amazing results are the beginning a new era in cervical cancer drug development and improved patient outcomes,” Mirza said. She underscored the “substantial unmet need for treatment options with durable responses in patients with advanced cervical cancer.”
Details of Survival Benefit
The second interim analysis was conducted at a median follow-up of 18.2 months when 85% of the total OS events had occurred.
The trial included 608 women (mean age, 51 years) with cervical cancer that had progressed after first-line platinum-based chemotherapy. The patients were enrolled in the multicenter study regardless of PD-L1 expression. They were randomly assigned in a 1:1 ratio to receive either cemiplimab 350 mg intravenously every 3 weeks or investigator’s choice of a single chemotherapy (pemetrexed, vinorelbine, gemcitabine, irinotecan, or topotecan) for up to 96 weeks.
The results show a median overall survival of 12.0 months with cemiplimab, vs 8.5 months with chemotherapy (hazard ratio [HR], 0.69).
Notably, the median OS was 11.1 months with cemiplimab, vs 8.8 months with chemotherapy (HR, 0.73) in a large subset of patients who had cervical squamous cell carcinoma (SCC). It was 13.3 months, vs 7.0 months, (HR, 0.56) in the smaller subset of patients who had adenocarcinoma.
“As you can see…the superiority of cemiplimab over chemotherapy in improving overall survival is apparent and significant in the squamous cell carcinoma population,” said Tewari.
He noted that these findings in the SCC population led to the IDMC recommendation to stop the study.
The SCC population accounted for the majority of the patients in both arms (239 of 304 patients taking cemiplimab and 238 of 304 patients receiving chemotherapy).
The OS findings in the adenocarcinoma population were “not part of the hierarchy” but were consistent with the data in the overall and SCC population, Tewari added.
The OS benefits were also apparent across prespecified subgroups based on geographic region, performance status, prior bevacizumab use, and number of prior lines of systemic therapy.
PFS and Other Endpoints
Progression-free survival (PFS) in both the overall and SCC population was 2.8 and 2.9 months with cemiplimab and chemotherapy, respectively (HR, 0.75 and 0.71) and 2.7 and 2.8 months, respectively, for the patients with adenocarcinoma (HR, 0.91), Tewari said.
Although the PFS appears similar for this secondary outcome measure, the overall PFS benefit was “driven by the tail of the curve,” he said. He explained that the curves separated at approximately 4 months for the overall and SCC populations and remained so.
In the adenocarcinoma population, there was a suggestion of PFS benefit, but this did not reach statistical significance.
Discussant Mirza agreed that considering the tail of the curve rather than the median PFS is important, inasmuch as it shows efficacy.
“That’s the beauty of immunotherapy,” he commented at the meeting. “Those who respond have very long-term benefit.”
It’s also important to note that the benefits are apparent in both the SCC and adenocarcinoma population, he said.
Investigator-assessed objective response rates were 16.4%, vs 6.3% overall; 17.6%, vs 6.7% for the SCC population; and 12.3%, vs 4.5% for the patients with adenocarcinoma. The overall estimated median duration of response was 16.4, vs 6.9 months, and the median observed time to response was 2.7, vs 1.6 months.
Cemiplimab was well tolerated, and no new safety signals were detected, Tewari commented.
Adverse events such as anemia, nausea, and vomiting, which occurred more often with cemiplimab than with chemotherapy, have previously been described for the PD-1/PD-L1 inhibitor class of drugs, he said.
In his discussion of the abstract, Mirza noted that, despite the promise of immunotherapy demonstrated in the trial, a substantial number of patients in the treatment arm experienced disease progression within 3 months, so this remains an unmet need.
The findings also raise questions to address in future studies, including how immunotherapy will perform in the first-line setting and whether results can be further improved with other novel agents, he noted.
The EMPOWER-CERVICAL trial was funded by Regeneron Pharmaceuticals, Inc, and Sanofi. Tewari reported financial relationships with Genentech, Tesaro, Clovis, AstraZeneca, Merck, AbbVie, Morphotek, and Regeneron Pharmaceuticals, Inc.
Ann Oncol. Published online May 12, 2021. Full text
ESMO Virtual Plenary: Abstract VP4-2021. Presented May 12, 2021.
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