Pembrolizumab increases survival of patients with unresectable cervical cancer on chemotherapy: NEJM
Pembrolizumab is a highly selective humanized monoclonal IgG4 antibody directed against the PD1 receptor on the cell surface. A new study by Dr Nicoletta Colombo, M.D reported that Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1) positive metastatic or unresectable cervical cancer that has progressed during chemotherapy.
The study is published in The New England journal of Medicine.
The objective of the study was to assess the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab.
The study was designed as a double-blinded, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. The dual primary end points were progression-free survival and overall survival, each tested sequentially in patients with a PD-L1 combined positive score of 1 or more, in the intention-to-treat population, and in patients with a PD-L1 combined positive score of 10 or more. The combined positive score is defined as the number of PD-L1–staining cells divided by the total number of viable tumor cells, multiplied by 100. All results are from the protocol-specified first interim analysis.
The results of the study were found to be
• A total of 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.50 to 0.77; P<0.001).
• In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P<0.001).
• In 317 patients with a PD-L1 combined positive score of 10 or more, progression-free survival was 10.4 months and 8.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.44 to 0.77; P<0.001).
• Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group (hazard ratio for death, 0.64; 95% CI, 0.50 to 0.81; P<0.001), 50.4% and 40.4% (hazard ratio, 0.67; 95% CI, 0.54 to 0.84; P<0.001), and 54.4% and 44.6% (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P=0.001).
• The most common grade 3 to 5 adverse events were anemia (30.3% in the pembrolizumab group and 26.9% in the placebo group) and neutropenia (12.4% and 9.7%, respectively).
Dr Colombo and team "Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab."
For further information: https://www.nejm.org/doi/full/10.1056/NEJMoa2112435
