Today, Professor A.M.M Eggermont presented the updated efficacy results of the phase III double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients with resected high-risk stage III melanoma.
Patients with stage III melanoma usually undergo surgery to remove the primary melanoma and the nearby metastasized lymph nodes. However, successful removal of melanoma through surgery, does not guarantee that patients will be cancer free. Pembrolizumab, an immune checkpoint inhibitor antibody, has been shown to stimulate the body’s immune system to remove remaining melanoma cells. After recovery from the lymph node surgery, the phase III double-blind EORTC 1325/KEYNOTE-054 study compared the administration of pembrolizumab and placebo, for a maximum of year. In 2018, at a 1.25-year median follow-up, this study showed that pembrolizumab treatment yielded a 43% reduction of their risk of melanoma recurrence or death as compared to placebo treatment, i.e. prolonging recurrence-free survival. These findings led to the approval of pembrolizumab for resected high-risk stage III melanoma patients by EMA in 2018 and by FDA in 2019.
In this study, 1019 patients were randomized to pembrolizumab (514 patients) or placebo (505 patients). A dose of 200 mg was given every three weeks for over a year or until there was disease recurrence or unacceptable toxicity. Two primary endpoints were assessed, recurrence free survival from randomization in the overall population and those patients with PD-L1 positive tumours. This abstract presents, a new, up-to-date evaluation of recurrence free survival at a 3-year median follow up.
Professor Eggermont showed that, adjuvant administration of pembrolizumab provided a sustained prolongation of recurrence free survival compared to placebo. In the overall population, the 3-year recurrence-free survival (RFS) rate was 64% (pembrolizumab group) vs 44% (placebo group). The improvement was consistent across all tumour and stage subgroups. Importantly, in BRAFmutant patients the RFS rate difference was 25% (62% vs 37%) and in BRAFwild type patients it was 16% (62%-46%), demonstrating a significant benefit irrespective of mutational status In the overall population, the 3-year cumulative incidence of distant metastasis as the first recurrence was 22% (pembrolizumab group) vs 37% (placebo group). These results confirm the clinical utility of pembrolizumab in the adjuvant setting in resected high-risk stage III melanoma.
“Pembrolizumab adjuvant therapy provides a clear and sustained relapse free survival benefit to stage III melanoma patients irrespective of stage subgroup or mutational status. We expect these benefits to be also consistent across endpoints at long term follow up” said Professor Alexander M.M. Eggermont, study chair of this study, Chief Scientific Officer and Professor of Surgical Oncology at Princess Máxima Center, Utrecht, The Netherlands