medwireNews: The final analysis of the phase III KEYNOTE-006 study shows continued survival benefits with pembrolizumab versus ipilimumab in patients with advanced melanoma.
Treatment with the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab resulted in twice as many patients alive and without disease progression at 2 years compared with the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab, with fewer side-effects, the researchers report.
Writing in The Lancet, Jacob Schachter (Sheba Medical Center, Tel Hashomer, Israel) and colleagues say that “pembrolizumab continues to show a clear and significant superiority compared with ipilimumab for patients with advanced melanoma, and [the findings] further support the use of pembrolizumab as a standard of care in this patient population.”
In total, 834 patients with advanced melanoma were enrolled into the multicenter KEYNOTE-006 study and randomly assigned to receive treatment with intravenous pembrolizumab 10 mg/kg every 2 weeks (n=279) or every 3 weeks (n=277) for a maximum of 2 years, or to receive intravenous ipilimumab 3 mg/kg every 3 weeks for four doses (n=278).
During a median follow-up period of 22.9 months, 383 patients died. Median overall survival (OS) was not reached in either pembrolizumab group and was 16.0 months in the ipilimumab group, which was equivalent to a significant 32% reduced risk for death with pembrolizumab.
In addition, pembrolizumab was associated with a 39% reduced risk for disease progression compared with ipilimumab; median progression-free survival (PFS) was 5.6 and 4.1 months among the patients receiving pembrolizumab every 2 and 3 weeks, respectively, and 2.8 months among those receiving ipilimumab.
At 24 months, the OS rate was 55% in both pembrolizumab groups compared with 43% in the ipilimumab group, while the PFS rate was 31% in the pembrolizumab 2-week group, 28% in the 3-week group, and 14% in the ipilimumab group.
Schachter and team also point out that “despite a three times longer duration of exposure, pembrolizumab continued to provide a favourable safety profile compared with ipilimumab.”
Grade 3–5 treatment-related toxicities occurred in 17% of patients receiving pembrolizumab compared with 20% of those receiving ipilimumab.
And the researchers explain that the type of adverse events differed between the treatment groups, due to their differing targets. Specifically, thyroid disorders were more common with pembrolizumab whereas colitis occurred more often in the patients given ipilimumab.
Based on these findings “it is reasonable to ask whether the use of ipilimumab should be discontinued,” Kilian Wistuba-Hamprecht and Graham Pawelec, both from University Medical Centre Tuebingen in Germany, remark in an accompanying comment.
However, they say that “promising results [are] now being reported for combined treatment with both anti-CTLA-4 and anti-PD-1 antibodies.”
“The main task for the future will be to better understand the mechanisms that underlie checkpoint inhibition with different antibodies against other targets, and to predict which patients will respond best to each regimen,” Wistuba-Hamprecht and Pawelec conclude.
By Laura Cowen
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