Follow-up analysis shows a 36% lower death hazard than placebo and no new safety signals associated with long-term use.
Adding pembrolizumab to chemotherapy continued to improve overall and progression-free survival in patients with persistent, recurrent, or metastatic cervical cancer after five years of follow-up, according to an exploratory analysis of the phase III KEYNOTE-826 trial.
The findings, published in JAMA Oncology, reinforce the role of pembrolizumab (Keytruda, Merck Sharp & Dohme Pty Ltd) plus platinum-based chemotherapy, with or without bevacizumab, as a first-line treatment option for advanced cervical cancer.
After a median follow-up of 59.1 months, patients who received pembrolizumab had a 36% lower hazard of death than those who received placebo alongside chemotherapy in the intention-to-treat population (HR 0.64, 95% CI 0.53–0.78).
The survival benefit was accompanied by a sustained improvement in progression-free survival, with a 39% lower hazard of disease progression or death in the pembrolizumab group (HR 0.61, 95% CI 0.51–0.74).
The analysis included 617 patients across 151 sites in 19 countries, with a median age of 51 years (range 22-82). Participants had previously untreated persistent, recurrent, or metastatic cervical cancer and were randomly assigned to pembrolizumab or placebo alongside chemotherapy, with bevacizumab permitted at the treating investigator’s discretion.
At five years, overall survival was 33.0% in the pembrolizumab group and 18.1% in the placebo group. Median overall survival was 26.4 months with pembrolizumab, compared with 16.8 months with placebo.
Progression-free survival at five years was 26.2% and 9.0%, respectively. Median progression-free survival was 10.4 months with pembrolizumab and 8.2 months with placebo.
Results were similar among patients whose tumours had a programmed death-ligand 1 (PD-L1) combined positive score of at least 1. In this subgroup, pembrolizumab was associated with an even lower hazard of death (HR 0.62, 95% CI 0.50–0.76) and disease progression or death (HR 0.58, 95% CI 0.48–0.71).
The five-year overall survival rate was 33.9% in the pembrolizumab arm, compared to 19.7% in the placebo arm, and the 5-year progression-free survival rate was 27.3% and 9.9%, respectively.
The authors noted that the survival curves remained separated throughout follow-up, with a plateau in progression-free survival from around 12 months onwards. This suggested that a subset of patients experienced prolonged disease control, although the findings do not establish that these patients were cured.
Related
The long-term safety profile remained consistent with earlier KEYNOTE-826 analyses, with no new safety signals identified and no additional deaths attributed to treatment-related adverse events since the final analysis.
Treatment-related adverse events were reported in 96.7% of patients receiving pembrolizumab and chemotherapy and 97.1% receiving placebo and chemotherapy. Grade 3 or higher treatment-related events occurred in 69.4% and 65.4%, respectively.
Immune-mediated adverse events or infusion reactions were more frequent with pembrolizumab, affecting 43.6% of patients compared with 29.8% in the placebo group. The most common immune-mediated events in the pembrolizumab group included hypothyroidism (19.2%), hyperthyroidism (8.1%), and colitis (5.2%).
Only one additional immune-mediated adverse event (low-grade thyroiditis) was reported in the pembrolizumab group after the previous final analysis.
The authors said the findings supported the durability of pembrolizumab’s survival benefit and its role in first-line treatment for advanced cervical cancer.
However, the analysis was exploratory and was not designed to redefine the trial’s original efficacy estimates. The authors cautioned that the results should be interpreted carefully, particularly for analyses involving smaller patient subgroups.
