Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma.

patients_and_methods

Patients were randomized to weekly intralesional daromun administrations (13 million IU of L19IL2 and 400 μg of L19TNF) for 4 weeks followed by surgery, or upfront surgery.

患者被随机分配到每周一次的局部注射daromun治疗（L19IL2 1300万国际单位和L19TNF 400微克），持续4周后进行手术，或者直接进行手术。

Pretreatment with approved adjuvant agents was allowed.

允许使用已批准的辅助治疗药物进行治疗前处理。

The primary endpoint was recurrence-free survival (RFS): events were disease recurrence or death from any cause after complete surgical tumor resection (ClinicalTrials.gov NCT02938299).

主要终点是无复发生存期（RFS）：事件定义为在完全手术切除肿瘤后疾病复发或任何原因导致的死亡（ClinicalTrials.gov NCT02938299）。

Results

A total of 246 patients were randomized and included in the intention-to-treatanalysis: 74% had undergone two or more prior surgical resections and 35% had received prior systemic therapy.

共有246名患者被随机分配并纳入意向治疗分析：其中74%的患者接受了两次或更多次的先前手术切除，35%的患者接受了先前的系统治疗。

At a median follow-up of 21 months, the neoadjuvant group (n = 122) had a significantly longer RFS than the upfront surgery group (n = 124), with a median RFS of 16.7 months and 6.8 months, respectively [hazard ratio(HR) 0.59, 95% confidence interval(CI 0.41-0.86), P = 0.005, log-rank test].

在中位随访21个月时，新辅助治疗组（n = 122）的无复发生存期（RFS）显著长于立即手术组（n = 124），中位RFS分别为16.7个月和6.8个月[风险比（HR）0.59，95%置信区间（CI 0.41-0.86），P = 0.005，对数秩检验]。

The risk of distant recurrence was reduced by 40% in the neoadjuvant arm (HR 0.60, 95% CI 0.37-0.95, P = 0.029).

新辅助治疗组远处复发的风险降低了40%（HR 0.60，95%置信区间0.37-0.95，P = 0.029）。

Grade ≥3 treatment-related adverse events (TRAEs) were 6.7% in the surgery-alone arm and 27.1% in the daromun arm, mostly injection site reactions.

仅手术组的3级及以上治疗相关不良事件（TRAEs）发生率为6.7%，而达罗木单抗组为27.1%，主要为注射部位反应。

Conclusions

Neoadjuvant daromun resulted in a significantly longer RFS than upfront surgery in patients with locally advanced melanoma.

新辅助达罗木单抗治疗在局部晚期黑色素瘤患者中显著延长了无复发生存期（RFS），与立即手术相比具有优势。

TRAEs were transient and manageable.

治疗相关不良事件（TRAEs）是暂时性的，并且是可管理的。

Neoadjuvant daromun is a new therapeutic option for patients with stage III melanoma, including those with locoregional recurrence after surgery and previous adjuvant therapy.

新辅助达罗木单抗为III期黑色素瘤患者提供了一种新的治疗选择，包括那些手术后出现局部区域复发以及之前接受过辅助治疗的患者。