Abstract：
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.
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.
摘要：
背景：尚未建立佐剂环境中粘膜黑素瘤（MM）的护理标准。同时,无复发生存期(RFS)仅在手术后5个月。这项II期试验旨在比较toripalimab与大剂量干扰素-α2b（HDI）作为切除MM的辅助疗法。
方法：从2017年7月至2019年5月，将145例切除的MM患者随机（1：1）接受HDI（n=72）或toripalimab（n=73）治疗1年，直至疾病复发/远处转移。不可接受的毒性，或撤回同意。主要终点是RFS。次要终点包括无远处转移生存期（DMFS），总生存期（OS），和安全。
结果：中位随访26.3个月后，RFS的数量，操作系统,在toripalimab臂和HDI臂中，DMFS事件分别为51对46，33对29和49对44，分别。toripalimab臂和HDI臂的中位RFS为13.6个月[95％置信区间（CI）8.31-19.02]和13.9个月（95％CI8.28-19.61），分别。两组之间的DMFS没有显着差异[风险比（HR）1.00；95％CI0.65-1.54]。toripalimab组的中位OS为35.1个月（95%CI27.93个月-未达到），两组的全因死亡无显著差异(HR1.11，95%CI0.66-1.84)。toripalimab臂和HDI臂患者实际输注剂量的中位数为3672mg和1054.5MIU，分别。在HDI组中，≥3级的治疗引起的不良事件的发生率远高于toripalimab组（87.5％对27.4％）。
结论：与HDI相比，Toripalimab显示出相似的RFS和更有利的安全性，都比历史数据好，这表明托里帕利马可能是更好的治疗选择。然而,仍需要进行更多的转化研究和更好的治疗方案,以改善MM的临床结局.
方法：从2017年7月至2019年5月，将145例切除的MM患者随机（1：1）接受HDI（n=72）或toripalimab（n=73）治疗1年，直至疾病复发/远处转移。不可接受的毒性，或撤回同意。主要终点是RFS。次要终点包括无远处转移生存期（DMFS），总生存期（OS），和安全。
结果：中位随访26.3个月后，RFS的数量，操作系统,在toripalimab臂和HDI臂中，DMFS事件分别为51对46，33对29和49对44，分别。toripalimab臂和HDI臂的中位RFS为13.6个月[95％置信区间（CI）8.31-19.02]和13.9个月（95％CI8.28-19.61），分别。两组之间的DMFS没有显着差异[风险比（HR）1.00；95％CI0.65-1.54]。toripalimab组的中位OS为35.1个月（95%CI27.93个月-未达到），两组的全因死亡无显著差异(HR1.11，95%CI0.66-1.84)。toripalimab臂和HDI臂患者实际输注剂量的中位数为3672mg和1054.5MIU，分别。在HDI组中，≥3级的治疗引起的不良事件的发生率远高于toripalimab组（87.5％对27.4％）。
结论：与HDI相比，Toripalimab显示出相似的RFS和更有利的安全性，都比历史数据好，这表明托里帕利马可能是更好的治疗选择。然而,仍需要进行更多的转化研究和更好的治疗方案,以改善MM的临床结局.
