Ipilimumab Plus Nivolumab Boost Metastatic Melanoma Survival

BRAF V600 mutation status does not significantly influence the efficacy of nivolumab in patients with advanced melanoma

medwireNews: Patients with stage III or IV unresectable melanoma benefit from nivolumab treatment regardless of BRAF V600 mutation status, shows a pooled analysis of four trials.

The objective response rate for patients given the anti-programmed death (PD)-1 antibody at a dose of between 0.1 and 10.0 mg/kg every 2 weeks was 34.6% for the 217 patients with BRAF V600 wild-type tumours and 29.7% for 74 patients with BRAF V600 mutations.

Response took a median time of 2.2 months for both groups and lasted for a median of 14.8 and 11.1 months in the patients with and without wild-type BRAF disease, respectively.

Of note, the objective response rate was not influenced by prior use of a BRAF inhibitor or the cytotoxic T lymphocyte-associated protein 4 inhibitor ipilimumab , or the melanoma’s programmed death ligand 1 status, write James Larkin, from the Royal Marsden Hospital in London, UK, and co-authors.

“Further prospective studies will be required to determine the optimal treatment schedule for BRAF/MEK inhibitors and immune checkpoint inhibitors in advanced melanoma”, they write in JAMA Oncology.

The risk of adverse events was comparable between those with and without wild-type BRAF melanoma, with any grade of toxicity reported in 68.3% and 58.5%, respectively, and grade 3 or 4 events in 11.7% and 2.8%.

The most common adverse events were fatigue, pruritus, rash and diarrhoea, affecting 5% or more of both groups.

Writing in an accompanying editorial, Tara Gangadhar and Lynn Schuchter, from the University of Pennsylvania in Philadelphia, USA, say “it is clear that patients both with and without BRAF-activating mutations gain benefit from PD-1 blockade, with durable responses observed in both subsets of patients, regardless of prior therapies.”

They therefore conclude that clinical trials of PD-1 blockade and combinations of targeted therapies “can be considered among the first line of therapy options for all patients with advanced melanoma”.


Larkin J, Lao CD, Urba WJ,et al. Efficacy and safety of nivolumab in patients withBRAFV600 mutant andBRAFwild-type advanced melanoma. A pooled analysis of 4 clinical trials. JAMA Oncol 2015; Advance online publication 21 May. doi:10.1001/jamaoncol.2015.1184

Gangadhar T, Schuchter LM. Broad applicability of nivolumab in melanoma regardless ofBRAFmutation status. JAMA Oncol 2015; Advance online publication 21 May. doi:10.1001/jamaoncol.2015.1237.

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