Efficacy of sunitinib in metastatic phaeochromocytomas and paragangliomas

So far, no randomised controlled trial in patients with metastatic phaeochromocytomas and paragangliomas has been published. The FIRSTMAPPP study, recently published on The Lancet, is the first to show safety and efficacy for sunitinib in these patients, supporting this multi-targeted receptor tyrosine kinase inhibitor as a potential candidate for first-line therapy.

The FIRSTMAPPP study is an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase II study; it’s the first in the field of patients with metastatic phaeochromocytomas and paragangliomas and one of the very few randomised controlled trials in the field of ultra-rare cancers. The study involved 78 patients with progressive metastatic phaeochromocytomas and paragangliomas, randomized to receive either oral sunitinib or placebo, chosen as the best control group in the absence of robust prospective data. The primary endpoint  was met, with a 12-month progression-free survival in 14 of 39 patients (36%) in the sunitinib group; in the placebo group, the 12-month progression-free survival in seven of 39 patients was 19%. The most frequent grade 3 or 4 adverse events were asthenia (18% and 3%), hypertension (13% and 10%), and back or bone pain (3% and 8%) in the sunitinib and placebo groups. Authors concluded that «As the first randomised controlled study in the field of patients with metastatic phaeochromocytomas and paragangliomas, FIRSTMAPPP is a major step forward to supporting sunitinib as the best validated treatment option and a potential candidate for first-line treatment in progressive metastatic phaeochromocytomas and paragangliomas. The placebo-control group study design used in FIRSTMAPPP does not allow the claim that sunitinib is superior to any other treatment option».