Pembrolizumab for Treatment of Patients with Advanced or Unresectable Melanoma
Cet article passe en revue les travaux récents sur le pembrolizumab, le premier anticorps anti PD-1 autorisé par la FDA pour le traitement des patients atteints d'un mélanome métastatique
From Coley's toxin to combination immune checkpoint inhibition, strategies to activate the immune system and generate anti-cancer immunity have been ongoing for well over a century. Over the past decade, the so-called immune checkpoint inhibitors, generally monoclonal antibodies that target key regulators of T-cell activation, emerged as the most effective immune targeted agents. Pembrolizumab is the first anti-programmed death 1 (PD-1) antibody approved by the FDA for the treatment of metastatic melanoma. With responses seen in 25-40% of patients, depending on dose and setting (i.e., before or after ipilimumab), pembrolizumab specifically and anti-PD-1 antibodies generally are revolutionizing the treatment of melanoma. However, in the setting of other recent advances in the field, a number of practical issues are emerging that need to be addressed to optimize the care of melanoma patients. First, the optimal sequencing of therapy (frontline immunotherapy over molecular targeted therapy, ipilimumab versus pembrolizumab as initial immune checkpoint inhibitor) is unknown and must be evaluated through randomized trials. Second, there is strong rational to combine immune checkpoint inhibitors (i.e., anti-PD-1 with ipilimumab) and to combine immune therapies with targeted therapy agents, so determining whether combination therapy is better than direct sequencing is another critical issue that needs to be addressed in carefully carried out studies.