Toripalimab vs Dacarbazine as First-Line Therapy for Advanced Melanoma of Acral Subtype: The Phase 3 MELATORCH Randomized Clinical Trial.

Background

To evaluate the efficacy and safety of toripalimab (a PD-1 inhibitor) vs dacarbazine as the first-line treatment in advanced melanoma predominantly of acral subtype.

评估toripalimab（一种PD-1抑制剂）与达卡巴嗪作为以肢端亚型为主的晚期黑色素瘤一线治疗的疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, positive-control phase 3 randomized clinical trial enrolled patients with advanced melanoma from January 22, 2018, to July 12, 2023.

设计、设置和参与者：这项多中心、开放标签、阳性对照的III期随机临床试验，从2018年1月22日至2023年7月12日，招募了晚期黑色素瘤患者。

Eligible patients had histologically confirmed stage III or IV melanoma and no prior systemic therapy for advanced melanoma.

符合条件的患者具有组织学证实的III期或IV期黑色素瘤，并且之前没有接受过晚期黑色素瘤的系统治疗。

Data were analyzed from September 23 to November 27, 2023.

数据分析时间为2023年9月23日至11月27日。

intervention

Patients were randomized (1:1) to receive toripalimab, 240 mg, every 2 weeks for up to 2 years, or dacarbazine, 1000 mg/m2, every 3 weeks until disease progression or intolerable toxic effects.

患者按1:1的比例随机接受toripalimab（每2周240毫克，最多2年）或 dacarbazine（每3周1000毫克/平方米），直至疾病进展或出现无法耐受的毒性反应。

Patients in the dacarbazine group were allowed to receive toripalimab after radiographic disease progression.

达卡巴嗪组的患者在放射学疾病进展后允许接受托瑞利单抗治疗。

main_outcomes_and_measures

Progression-free survival(PFS) assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors, version 1.1.

通过盲法独立中央审查（BICR）根据实体瘤反应评估标准（版本1.1）评估无进展生存期（PFS）。

Results

The analysis included 256 patients (median [range] age, 58 [18-85] years; 113 females [44.3%] and 142 males [55.7%]), among whom 160 participants (62.7%) had acral melanoma; 127 were randomized to receive toripalimab and 128 to dacarbazine (1 patient was excluded for Good Clinical Practice violation).

分析纳入了256名患者（中位年龄[范围]，58[18-85]岁；113名女性[44.3%]和142名男性[55.7%]），其中160名参与者（62.7%）患有肢端黑色素瘤；127名被随机分配接受托瑞利单抗治疗，128名接受达卡巴嗪治疗（1名患者因违反良好临床实践规范被排除）。

The median (range) follow-up period was 11.8 (0.1-62.5) months.

随访中位时间（范围）为11.8（0.1-62.5）个月。

Toripalimab significantly reduced the risk of disease progression or death by 29.2% (hazard ratio, 0.71; 95% CI, 0.53-0.95; P = .02) compared with dacarbazine as assessed by BICR .

托瑞利珠单抗显著降低了疾病进展或死亡的风险，降低了29.2%（风险比，0.71；95%置信区间，0.53-0.95；P = .02），与达卡巴嗪相比，这是通过BICR评估得出的。

Consistent PFS benefit was observed in most predefined subgroups, including patients with acral subtype.

在大多数预先定义的亚组中观察到一致的无进展生存（PFS）获益，包括具有肢端亚型的患者。

The BICR-assessed objective response rateof 11.0% (95% CI, 6.2%-17.8%) vs 8.6% (95% CI, 4.4%-14.9%), and the median duration of response of 13.8 (95% CI, 5.9-not evaluable) months vs 6.9 (95% CI, 3.8-not evaluable) months, respectively, also favored toripalimab over dacarbazine.

BICR评估的客观缓解率为11.0%（95%置信区间，6.2%-17.8%）对比8.6%（95%置信区间，4.4%-14.9%），以及缓解持续时间的中位数为13.8个月（95%置信区间，5.9-未评估）对比6.9个月（95%置信区间，3.8-未评估），这些数据也倾向于toripalimab优于 dacarbazine。

Grade 3 or worse treatment-related adverse events occurred in 36 patients (28.3%) receiving toripalimab, with the most common (≥3%) being increased lipase (11 patients [8.7%]), anemia (5 patients [3.9%]), increased γ-glutamyltransferase (4 patients [3.1%]), hyponatremia (4 patients [3.1%]), and increased blood triglycerides (4 patients [3.1%]).

在接受toripalimab治疗的36名患者（28.3%）中发生了3级或更严重的治疗相关不良事件，最常见的（≥3%）为增加的脂肪酶（11名患者[8.7%]），贫血（5名患者[3.9%]），增加的γ-谷氨酰转移酶（4名患者[3.1%]），低钠血症（4名患者[3.1%]）和增加的血甘油三酯（4名患者[3.1%]）。

conclusions_and_relevance

This phase 3 randomized clinical trial found that as a first-line treatment for advanced melanoma predominantly of acral subtype, toripalimab showed a significant PFS benefit over dacarbazine and an acceptable safety profile.

这项III期随机临床试验发现，作为主要针对肢端亚型晚期黑色素瘤的一线治疗，托瑞利珠单抗相比达卡巴嗪显示出显著的无进展生存期（PFS）优势，并具有可接受的安全性。

trial_registration

ClinicalTrials.gov Identifier: NCT03430297.

ClinicalTrials.gov注册号：NCT03430297。