Mucosal melanoma (MM) is rare in the West, but in Asia it is the second most common melanoma subtype, accounting for about a quarter of all melanomas. MM has genetic features and biological behaviors that are distinct from cutaneous melanoma and has a much worse prognosis, with a 5-year survival rate of 25% versus 80% for cutaneous melanoma. While adjuvant immune checkpoint inhibitors (ICIs; anti-PD1) are now the standard of care for patients with cutaneous melanoma, no standard adjuvant treatment has been established for localized MM after surgery, representing a high unmet need. Previous trials in early-stage melanoma, including MM, have shown adjuvant high-dose interferon-α2b (HDI) may improve outcomes. Also, in metastatic MM, ICIs appear to be effective, though less so than in cutaneous melanoma.

Investigators from China conducted a phase II randomized trial comparing HDI with the anti-PD1 toripalimab in patients with completely resected MM. In total, 145 patients received either HDI or toripalimab for 1 year or until disease recurrence or intolerable toxicity. Patients were enrolled at a median time of 14.3 weeks after surgery and were stratified according to disease stage (I – III), primary tumor site (head and neck or non-head and non-neck), and PD-L1 expression status. Patients with MM in the head and neck (39.3%) also received adjuvant radiotherapy within 6 – 8 weeks after the first treatment. The primary endpoint was relapse-free survival (RFS) in all randomized patients, and the secondary endpoints included distant metastasis-free survival (DMFS), OS, and safety. At median follow-up of 26.3 months, the median RFS was similar in both arms: 13.9 months with HDI and 13.6 months with toripalimab (hazard ratio [HR], 1.05; P = 0.812). Of interest, the median RFS of PD-L1-positive patients were 11.1 months in the HDI arm and 17.4 months in the toripalimab arm, although the difference was not statistically significant. Similarly, no significant differences in RFS were observed across other subgroups. DMFS was not significantly different: 14.6 months with HDI vs. 16.3 months with toripalimab (HR, 1.00). Median OS was not reached with HDI and was 35.1 months with toripalimab (HR, 1.1). The authors speculate that subsequent treatment with ICIs after HDI may contribute to this result. Of note, toripalimab had a better safety profile than HDI. The incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was much higher with HDI than with toripalimab (87.5% vs. 27.4%). The majority of toripalimab TEAEs were grade 1 or 2, and the most common TEAE was an elevated thyroid-stimulating hormone level (49.3%). Among patients receiving HDI, the most common TEAE was myelosuppression (any grade: 98.6%; grade ≥3: 59.7%). In addition, HDI was associated with higher incidence of pyrexia and elevation of liver transaminases. Treatment discontinuation due to TEAEs were similar in both arms (around 8%), although dose delay was more common with HDI (20.8% vs. 13.7%). There were no treatment-related deaths or infusion reactions.

“Toripalimab had a more favorable safety and tolerability profile than HDI, suggesting that toripalimab might be the better treatment option,” the authors wrote. However, they acknowledged several limitations to the study and commented that additional translational studies and biomarker research are needed to confirm their findings, as well as improved toripalimab regimens.

Reference:
Lian B, et al. Ann Oncol. 2022, July 13 [Online ahead of print].