BACKGROUND: Adjuvant therapy plays a critical role in the treatment of oral mucosal melanoma (OMM). Anti-programmed cell death-1 (PD-1) agents are recommended as front-line therapy for metastatic melanoma, but their efficacy as adjuvant therapy for high-risk OMM remains unclear.
METHODS: A single-center, retrospective cohort study was conducted in 193 nodular-type oral mucosal melanoma (NOMM) patients who received chemotherapy alone or in combination with high-dose interferon-α2b (HDI) or anti-PD-1 agents as adjuvant therapy. Multivariate analysis was performed to identify significant prognostic factors for the 2-year overall survival (OS) and progression-free survival (PFS).
RESULTS: Tumor thickness, ulceration and invasion level were found to be independent prognostic factors for both 2-year OS and PFS, while T-stage was only associated with OS. The 2-year OS and PFS were 43.5% and 10.9% in patients who received only chemotherapy. In comparison, the 2-year OS was improved, albeit not significantly (47.4%; p > 0.05), and PFS was significantly improved (43.6%; p = 0.0028) in patients who received chemotherapy plus HDI; and both 2-year OS (71.0%; p = 0.0118) and PFS (53.6%; p = 0.0001) were significantly improved in patients received chemotherapy plus anti-PD-1. The serious adverse event (SAE) (p < 0.0001) and discontinued treatment due to SAE (p < 0.0001) were significantly lower in patients who received anti-PD-1 than in patients who received HDI.
CONCLUSIONS: Invasion level and tumor thickness are independent prognostic factors for NOMM. Chemotherapy plus anti-PD-1 agents seem to be the adjuvant therapy of choice for NOMM, as it is safer and more tolerable than HDI and, more importantly, it can significantly improve the OS and PFS.

BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM.
METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety.
RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients\' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%).
CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.