The combination of nivolumab and ipilimumab appeared safe and effective in patients with mucosal melanoma, according to a pooled analysis.

Although mucosal melanomas are rare, prognosis for patients is poor, Sandra P. D’Angelo, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues wrote.

“Mucosal melanoma is an aggressive subtype that is largely resistant to traditional therapies,” they added.

“A major challenge with mucosal melanoma is that well-established protocols for staging and treatment are lacking, and in the absence of discernable signs or symptoms recognizable by the patient, diagnosis often occurs at late stages.”

The combination of nivolumab (Opdivo, Bristol-Meyers Squibb) — a PD-1 checkpoint inhibitor — plus ipilimumab (Yervoy, Bristol-Meyers Squibb) — a CTLA-4 checkpoint inhibitor — has been found to safely and effectively treat melanoma.

However, limited research has been conducted for the combination’s use in the treatment of other melanoma subtypes.

D’Angelo and colleagues evaluated pooled data from six clinical trials of patients with advanced melanoma — including:

889 patients who received nivolumab monotherapy (mucosal melanoma, n = 86; cutaneous melanoma, n = 665);
407 patients treated with nivolumab plus ipilimumab (mucosal melanoma, n = 35; cutaneous melanoma, n = 326); and
357 patients who received ipilimumab monotherapy (mucosal melanoma, n = 36; cutaneous melanoma, n = 269).

In patients with mucosal melanoma, those who received the combination demonstrated longer PFS (5.9 months; 95% CI, 2.2 to not reached) compared with those who received nivolumab monotherapy (3 months; 95% CI, 2.2-5.4 months) or ipilimumab monotherapy (2.7 months; 95% CI, 2.6-2.8 months).

ORR also was higher among patients with mucosal melanoma who received the combination (37.1%; 95% CI, 21.5-55.1) compared with nivolumab (23.3%; 95% CI, 14.8-33.6) and ipilimumab (8.3%; 95% CI, 1.8-22.5) alone.

Patients with cutaneous melanoma also experienced longer PFS with combination therapy (11.7 months; 95% CI, 8.9-16.7) than with nivolumab (6.2 months; 95% CI, 5.2-7.5) and ipilimumab (3.9 months; 95% CI, 2.9-4.4) monotherapy. The combination also conferred superior ORR (60.4%; 95% CI, 54.9-65.8) compared with nivolumab (40.9%; 95% CI, 37.1-44.7) and ipilimumab (21.2%; 95% CI, 16.5-26.6) monotherapy in patients with cutaneous melanoma.

The magnitude of differences in ORR between patients with PD-L1 expression of 5% or more and those with PD-L1 expression of less than 5% were greater for patients with mucosal melanoma than those with cutaneous melanoma.

Fewer patients with mucosal than cutaneous melanoma experienced grade 3 or grade 4 treatment-related adverse events with nivolumab monotherapy (8.1% vs. 12.5%) and combination therapy (40% vs. 54.9%).

Rates of discontinuation due to treatment-related adverse events also were lower in patients with mucosal melanoma who received nivolumab monotherapy (2.3% vs. 3.9%) and combination therapy (17% vs. 31%).

“Patients may benefit from anti–PD-1-based therapy regardless of the presence of poor prognostic factors, tumor PD-L1 expression and prior therapy,” D’Angelo and colleagues wrote.

“The results of our analyses, pending mature OS data, suggest that nivolumab alone and in combination with ipilimumab are promising treatment options for mucosal melanoma.” – by Kristie L. Kahl


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