5-year results for pembrolizumab treatment of advanced melanoma
Mené sur 834 patients adultes atteints d’un mélanome de stade avancé (durée de suivi : 5 ans), cet essai randomisé multicentrique de phase III compare l’efficacité, du point de vue de la survie globale et de la survie sans progression, et la toxicité du pembrolizumab et de l'ipilimumab
Current standard practice is to use checkpoint inhibitors for the treatment of patients with metastatic melanoma. The cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) antibody ipilimumab was the first drug that was shown to improve the survival of patients with metastatic melanoma. Although the proportions of patients who achieved a response were low (only 10–20%), approximately 20% of patients achieved long-term tumour control. These findings gave rise to hopes of being able to even cure patients with advanced melanoma. The KEYNOTE-006 randomised phase 3 trial, reported by Caroline Robert and colleagues in The Lancet Oncology, has shown that the PD-1 antibody pembrolizumab is more effective than ipilimumab, with 235 (42%) of 556 patients assigned to pembrolizumab achieving an objective response versus 46 (17%) of 278 patients assigned to ipilimumab, median progression-free survival of 8·4 months versus 3·4 months, and overall survival of 32·7 months versus 15·9 months, respectively. These results for pembrolizumab are similar to those recorded for patients on nivolumab monotherapy; however, the combination of ipilimumab and nivolumab currently seems to be the most effective immunotherapy for melanoma, especially among distinct subgroups of patients with a PD-L1-negative tumour, high tumour load, or brain metastases. Additionally, BRAF or MEK inhibition is a possible alternative for patients with BRAF-mutant melanoma. Hence, an individualised first-line treatment decision should be made for every patient based on their clinical situation.
The Lancet Oncology 2019