PD-1 Therapy Shows Promise For Acral, Mucosal, Select Uveal Melanoma Patients

Preliminary findings suggest potential for programmed cell death protein 1 inhibitor therapy in acral and mucosal melanoma and perhaps uveal disease

medwireNews: Research suggests that patients with acral and mucosal melanoma may benefit from programmed cell death protein 1 (PD-1) inhibitor therapy, while a small subset of patients might respond to treatment for uveal melanoma.

The first of two cohort analyses published in Cancer describes the outcome of 25 patients with advanced acral melanoma and 35 with advanced mucosal melanoma, the majority of whom had undergone prior treatment, including with the CTLA-4 inhibitor ipilimumab.

Forty patients were treated with pembrolizumab 2 mg/kg or 10 mg/kg every 2–3 weeks, while 20 received nivolumab 0.3–10 mg/kg on a similar schedule, report Alexander Shoushtari, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-authors.

Treatment achieved a RECIST objective response rate of 32% for the acral melanoma patients, including two complete responses and six partial responses, and 23% for those with mucosal melanoma, with eight patients achieving a partial response.

The acral and mucosal melanoma groups were followed up for a median of 20.0 months and 10.6 months, respectively, and achieved median progression-free survival (PFS) of 4.1 months and 3.9 months.

Noting that just two patients discontinued therapy because of side effects, the authors say “the results support the routine use of these agents for these rare melanoma subtypes”.

They recommend further investigation into newer treatment combinations, such as ipilimumab plus nivolumab, as well as research into driver mutations, biomarkers and immunological infiltrates in acral and mucosal melanoma.

By contrast, the authors of a second study reviewing the clinical outcome of PD-1 and programmed death-ligand 1 (PD-L1) targeted therapy in 56 patients with stage IV uveal melanoma found the agents “rarely confer durable remissions”.

Most of the patients had undergone at least one prior therapy, including ipilimumab in 63%, before beginning treatment with pembrolizumab (n=38), nivolumab (n=16) or the PD-L1 inhibitor atezolizumab (n=2).

PD-1 and PD-L1 therapy was well tolerated, with just one patient discontinuing treatment for toxicity, but none of the patients achieved a RECIST complete response and just five had stable disease lasting 6 months or longer, say Alain Algazi, from the University of California, San Francisco, USA, and fellow investigators.

However, the first of the two patients to achieve a partial response continues to respond to nivolumab therapy after 46 cycles and 23 months of therapy, while the second patient has maintained a response to pembrolizumab after 39 cycles and 27 months of treatment.

Median PFS in the cohort is 2.6 months, but five patients remain free from progression after a median of 13.8 months, the team adds.

“These data suggest that the preferred front-line therapy for advanced uveal melanoma should remain clinical trial participation”, the authors write, emphasizing the need for research into predictive biomarkers and the mechanisms of response and progression in uveal melanoma.

But acknowledging that an immunosuppressive tumour environment may limit PD-1 or PD-L1, they conclude that “uveal melanoma simply may be a cancer that will not easily be targeted by immune therapy and will require alternate approaches based on our evolving understanding of its biology.”

References

Shoushtari AN, Munhoz RR, Kuk D, et al. The efficacy of anti-PD-1 agents in acral and mucosal melanoma. Cancer; Advance online publication 17 August 2016

DOI: 10.1002/cncr.30259

Algazi AP, Tsai KK, Shoushtari AN, et al. Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-1L [WLSH1] antibodies. Cancer 2016; Advance online publication 17 August 2016

DOI: 10.1002/cncr.30258

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