Immunotherapy enters first-line treatment regimen for advanced cervical cancer
Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385:1856-1867.
Persistent, recurrent, and metastatic cervical cancer carries a very poor prognosis: Most patients progress less than a year after starting treatment, and fewer than half survive for 2 years. First-line treatment in this setting has been platinum-based chemotherapy, often given with bevacizumab, a humanized monoclonal antibody that inhibits tumor growth by blocking angiogenesis.8 Pembrolizumab, an immune checkpoint inhibitor, targets cancer cells by blocking their ability to evade the immune system, and it is FDA approved and widely administered to patients with advanced cervical cancer who progress after first-line treatment.9
Addition of pembrolizumab extended survival
In the KEYNOTE-826 trial, Colombo and colleagues investigated the efficacy of incorporating an immune checkpoint inhibitor into the first-line treatment regimen for patients with persistent, recurrent, and metastatic cervical cancer.10 Researchers in this double-blinded, phase 3, randomized controlled trial assigned 617 patients to receive pembrolizumab or placebo concurrently with the investigator’s choice platinum-based chemotherapy. Bevacizumab was administered at the discretion of the treating oncologist.
The proportion of patients who survived at least 2 years following randomization was significantly higher among those assigned to pembrolizumab compared with placebo (53% vs 42%; HR, 0.67, 95% CI, 0.54–0.84).10 Similarly, median progression-free survival was superior among patients who received pembrolizumab compared with those who received placebo (10.4 months vs 8.2 months; HR, 0.65; 95% CI, 0.53–0.79). The role of bevacizumab in conjunction with pembrolizumab and platinum-based chemotherapy was not elucidated in this study because bevacizumab administration was not randomly assigned.
Anemia and neutropenia were the most common adverse events and were more frequent in the pembrolizumab group, but there were no new safety concerns related to concurrent use of pembrolizumab with cytotoxic chemotherapy and bevacizumab. Importantly, subgroup analysis results suggested that pembrolizumab was effective only in patients whose tumors expressed PD-L1 (programmed death ligand 1), a biomarker of pembrolizumab sensitivity in cervical cancer.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
In light of the significant improvements in overall and progression-free survival demonstrated in the KEYNOTE-826 trial, in October 2021, the FDA approved the use of frontline pembrolizumab alongside platinum-based chemotherapy, with or without bevacizumab, for treatment of patients with persistent, recurrent, or metastatic cervical cancers that express PD-L1.
In light of the significant improvements in overall and progression-free survival demonstrated in the KEYNOTE-826 trial, in October 2021, the FDA approved the use of frontline pembrolizumab alongside platinum-based chemotherapy, with or without bevacizumab, for treatment of patients with persistent, recurrent, or metastatic cervical cancers that express PD-L1.
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