Nivolumab Plus Ipilimumab Improves Response in Metastatic Melanoma Patients

Patients with metastatic melanoma derive a significant response benefit from the first-line nivolumab and ipilimumab combination compared with ipilimumab monotherapy

medwireNews: Addition of nivolumab to ipilimumab boosts the objective response rate (ORR) and progression-free survival (PFS) in patients with metastatic melanoma, according to research published in The New England Journal of Medicine.

In this double-blind trial comprising treatment-naïve patients with unresectable stage III or IV disease, combination treatment benefited not only patients with BRAF Wild-type tumours, but also those carrying the BRAF V600 mutation, the team reports.

In the group of patients with BRAF wild-type tumours, the investigator-assessed ORR was significantly higher in the 72 participants randomly assigned to receive the PD-1 inhibitor nivolumab plus the anti-CTLA-4 Antibody ipilimumab than in the 37 patients treated with ipilimumab alone, at 61% versus 11%.

A complete response was achieved by 16 patients in the dual therapy group and by no patients in the monotherapy group.

Moreover, median PFS was not reached in the combination therapy arm and was 4.4 months in the monotherapy arm, giving a significant hazard ratio for disease progression or death of 0.40 with the combination therapy.

Among those with the BRAF V600 mutation, the investigator-assessed ORR was 52% in the nivolumab plus ipilimumab group (n=23) and 10% in the ipilimumab alone group (n=10), with respectively five and no patients achieving a complete response. And median PFS was 8.5 months and 2.7 months in the combination and monotherapy arms, respectively.

Drug-related grade 3 or 4 adverse events were observed in 54% of study participants given nivolumab plus ipilimumab and in 24% of those given ipilimumab alone.

Colitis and diarrhoea were the most frequent toxicities in either treatment arm, observed respectively in 17% and 11% of patients in the combination therapy group and in 11% and 7% of those in the monotherapy group.

Almost half the patients in the nivolumab plus ipilimumab group discontinued treatment as a result of toxic effects, but joint senior investigators Jedd Wolchok, from Memorial Sloan Kettering Cancer Center in New York, USA, and F Stephen Hodi, from Dana–Farber Cancer Institute in Boston, Massachusetts, USA, and co-authors point out that of these patients, “68% had an objective response and most continue to have a response”.

They conclude: “The risk–benefit profile of combined PD-1 and CTLA-4 blockade, as compared with monotherapy, will be further clarified by data from ongoing phase 3 double-blind, randomized trials, such as the CheckMate 067 study.”

Reference

Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma. N Engl J Med; Advance online publication 20 April 2015. doi:10.1056/NEJMoa1414428

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