Toripalimab (anti-PD-1) versus high-dose interferon-a2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial
Toripalimab (anti-PD-1) versus high-dose interferon-a2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial
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DOI：
10.1016/j.annonc.2022.07.002
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发表时间：
2022-10-10
影响因子：
50.5
通讯作者：
Cui, C. L.
中科院分区：
文献类型：
--
作者：
Lian, B.;Si, L.;Cui, C. L.
背景：尚未建立粘膜黑色素瘤（MM）辅助治疗的标准。同时，单纯手术后无复发生存期（RFS）仅为5个月。该II期试验旨在比较toripalimab与高剂量干扰素-a2 b（HDI）作为切除的MM的辅助疗法。患者和方法：从2017年7月至2019年5月，145名切除的MM患者被随机分组（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知情同意。主要终点为RFS。次要终点包括无远处转移生存期（DMFS）、总生存期（OS）和安全性。结果如下：中位随访26.3个月后，toripalimab组和HDI组的RFS、OS和DMFS事件数量分别为51与46、33与29和49与44。Toripalimab组和HDI组的中位RFS分别为13.6 [95%置信区间（CI）8.31-19.02]个月和13.9（95% CI 8.28-19.61）个月。两组之间的DMFS无显著差异[风险比（HR）1.00; 95% CI 0.651.54]。toripalimab组的中位OS为35.1个月（95%CI 27.93个月-未达到），两组的全因死亡无显著差异（HR 1.11，95%CI 0.66-1.84）。在toripalimab组和HDI组中，患者实际输注剂量的中位总和分别为3672 mg和1054.5 MIU。HDI组中>3级的治疗后出现的不良事件的发生率远高于Toripalimab组（87.5% vs 27.4%）。结论：Toripalimab显示出与HDI相似的RFS和更有利的安全性特征，均优于历史数据，表明Toripalimab可能是更好的治疗选择。然而，更多的转化研究和更好的治疗方案仍然是必要的，以改善MM的临床结果。
Background: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only w5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-a2b (HDI) as an adjuvant therapy for resected MM. Patients and 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 0.651.54]. 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.