Nivolumab Shows Promise in Mucosal Melanoma

Nivolumab alone or in combination with ipilimumab are promising treatment options for patients with mucosal melanoma, according to a new study.

Nivolumab alone or in combination with ipilimumab are promising treatment options for patients with mucosal melanoma, according to a new study presented at the Society for Melanoma Research 2015 International Congress, held November 18–21 in San Francisco.

Mucosal melanoma is a rare but aggressive melanoma subtype that is more resistant to treatment than cutaneous melanoma, said Dr. James Larkin, medical oncologist at the Royal Marsden Hospital in London. In patients with metastatic mucosal melanoma, the CTLA-4 immune checkpoint inhibitor ipilimumab has demonstrated response rates in the range of 7% to 12%, a median progression-free survival (PFS) of 2.7 to 4.3 months, and a median overall survival of 6.4 months.

Dr. Larkin and colleagues conducted a pooled analysis of data from six trials of metastatic melanoma patients who received the programmed death-1 (PD-1)-inhibitor nivolumab, ipilimumab, or a combination of the two. Among the 889 patients treated, 86 patients with mucosal melanoma were treated with nivolumab, 36 mucosal melanoma patients were treated with ipilimumab, and 35 patients with mucosal melanoma were treated with the combination.

Programmed death ligand-1 (PD-L1) positivity was observed in about one-third of the cutaneous melanoma patients and about one-quarter of the mucosal melanoma patients, noted Dr. Larkin.

The exploratory median PFS for mucosal melanoma patients was 6 months with the combination and 3 months with the single agents after a median follow-up of 6 to 8 months. The median PFS for the cutaneous group was slightly higher-12 months for the combination, 6 months for nivolumab, and 4 months for ipilimumab.

The overall response rate (ORR) in the mucosal melanoma patients was 37% with combined treatment, 23% with nivolumab, and 8.3% with ipilimumab. The median duration of response has not been reached with the combination or nivolumab and is 2.4 months with ipilimumab.

Some 85% of patients who responded to the combination or to nivolumab have ongoing responses. “Most of these patients responded early and are still on treatment after about 1 year,” Dr. Larkin said.

An analysis of PFS and ORR by subgroups, including age, gender, baseline ECOG performance status, M stage at study entry, and baseline LDH, found the combination and nivolumab were superior to ipilimumab and “the combination appears to be superior to nivolumab in most subgroups,” he said.

Among patients with a high expression of PD-L1, the median PFS was not reached with the combination, was 12 months with nivolumab, and was 3 months with ipilimumab. Those with low PD-L1 expression had 2 to 3 months PFS in all treatment groups.

“For both mucosal and cutaneous melanoma, nivolumab plus ipilimumab resulted in a numerically higher ORR vs nivolumab alone, regardless of PD-L1 expression,” Larkin said.

He noted that the types and frequencies of treatment-related adverse events were generally similar between cutaneous and mucosal melanoma subtypes.

In conclusion, Dr. Larkin said: “This pooled analysis represents the largest report of efficacy and safety outcomes for patients with mucosal melanoma treated with anti–PD-1 therapy. Nivolumab combined with ipilimumab consistently showed a clinically meaningful improvement in PFS and ORR as compared to nivolumab or ipilimumab alone. Efficacy results were consistent across patient subgroups for both mucosal and cutaneous melanoma.”