Cemiplimab extends survival vs. chemotherapy in recurrent cervical cancer
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Cemiplimab extended OS compared with single-agent chemotherapy for women with recurrent cervical cancer, according to randomized phase 3 study results published in The New England Journal of Medicine.
Researchers characterized the OS benefit as “significant and clinically meaningful.”
Rationale
Women with recurrent cervical cancer have a poor prognosis, according to Krishnansu Tewari, MD, associate professor in the division of gynecologic cancer at University of California, Irvine, and colleagues.
Cemiplimab (Libtayo; Regeneron Pharmaceuticals, Sanofi) is a fully human PD-1-blocking antibody approved in the United States to treat certain patients with lung or skin cancers.
Prior studies showed the agent demonstrated preliminary clinical activity among women with recurrent cervical cancer.
“Although patients treated with chemoradiation plus bevacizumab [Avastin, Genentech] have a survival benefit, they are not cured and most, if not all, will ultimately progress,” Tewari told Healio. “The management of second-line therapy following progression on platinum therapy with or without bevacizumab is a high unmet need, and prior work suggested that the PD-1/PD-L1 axis may be an important therapeutic target.”
Methodology
Tewari and colleagues enrolled 608 women (median age, 51 years) with recurrent cervical cancer who had progressed after first-line platinum-containing chemotherapy, regardless of PD-L1 status.
Most study participants (77.8%) had squamous cell carcinoma, and 22.2% had adenocarcinoma or adenosquamous carcinoma.
Researchers randomly assigned women 1:1 to cemiplimab dosed at 350 mg every 3 weeks (n = 304) or investigator’s choice of chemotherapy (n = 304).
OS served as the primary endpoint. Secondary endpoints included PFS and safety.
Investigators reported longer median duration of treatment exposure in the cemiplimab group (15.2 weeks vs. 10.1 weeks).
Key findings
Median follow-up was 18.2 months.
At data cutoff, 199 women (65.5%) assigned cemiplimab and 229 (75.3%) assigned chemotherapy had discontinued treatment due to disease progression. Thirty-seven women (12.2%) continued to receive cemiplimab treatment, one (0.3%) continued receiving cemiplimab retreatment, and seven (2.3%) continued to receive chemotherapy.
Researchers reported longer median OS among women assigned cemiplimab (12 months vs. 8.5 months; HR = 0.69; 95% CI, 0.56-0.84).
The OS benefit appeared consistent in clinically relevant subgroups, including women with adenocarcinoma or adenosquamous carcinoma, as well as those who previously received bevacizumab (Avastin, Genentech).
Results also showed benefit with cemiplimab with regard to PFS (HR = 0.75; 95% CI, 0.63-0.89) and objective response rate (overall population, 16.4% vs. 6.3%; PD-L1 expression 1% or greater, 18% vs. 1%). Eleven percent of women with PD-L1 expression less than 1% responded to cemiplimab.
Cemiplimab exhibited a safety profile consistent with prior studies.
Grade 3 or higher adverse events occurred among 45% of women assigned cemiplimab and 53.4% of those assigned chemotherapy. The most common grade 3 or higher adverse events included anemia (12% with cemiplimab vs. 26.9% with chemotherapy), urinary tract infection (5% vs. 2.8%) and neutropenia (1% vs. 9%).
Implications
“This study provides a proof of concept of immunotherapeutic checkpoint inhibition in cervical cancer. If cemiplimab is approved, it will provide a second-line treatment option for women with recurrent cervical cancer,” Tewari said. “Studies are ongoing combining anti-TIGIT with anti-PD-1, and other studies evaluating the combinations of antibody-drug conjugates with other novel medicines are also underway.”
For more information:
Krishnansu Tewari, MD, can be reached at ktewari@uci.edu.
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