Efficacy and Safety of Ultra-Low-Dose Immunotherapy in Relapsed Refractory Solid Tumors: Phase III Superiority Randomized Trial (DELII).

We hypothesized that ultra-low-dose nivolumab would retain clinical efficacy.

我们假设超低剂量的纳武利尤单抗将保持临床疗效。

patients_and_methods

In this phase III randomized superiority trial, patients with advanced solid tumors (Eastern Cooperative Oncology Group 0-1) and progression on ≥1 prior line of systemic therapy were randomly assigned 1:1 to ultra-low-dose nivolumab (20 mg intravenously once every 2 weeks) or standard chemotherapy (docetaxel or paclitaxel, as per tumor type).

在这项III期随机优效试验中，患有晚期实体瘤（东部肿瘤协作组0-1级）且在≥1线系统治疗后进展的患者被随机1:1分配至超低剂量纳武利尤单抗（每2周静脉注射20毫克）或标准化疗（根据肿瘤类型，使用多西他赛或紫杉醇）。

Treatment continued until progression or intolerable toxicity.

治疗将持续进行，直至疾病进展或出现无法耐受的毒性。

The primary end point was overall survival(OS).

主要终点是总生存（OS）。

Results

From June 2020 to February 2024, we enrolled 500 patients: 250 per arm; 52% had head and neck and 36% lung cancers.

从2020年6月至2024年2月，我们共招募了500名患者：每组250名；其中52%患有头颈部癌症，36%患有肺癌。

The median number of prior lines of therapy was 1 (range, 1-8); 29% had received ≥2 prior lines.

先前治疗线数的中位数为1（范围，1-8）；29%的患者接受了≥2条先前治疗线。

Median OS was significantly longer with ultra-low-dose nivolumab: 5.88 months (95% CI, 4.99 to 7.13) versus 4.70 months (95% CI, 3.91 to 5.65; hazard ratio[HR], 0.80 [95% CI, 0.66 to 0.97]; P = .022).

使用超低剂量纳武利尤单抗的中位总生存期显著更长：5.88个月（95% 置信区间，4.99 至 7.13）对比 4.70 个月（95% 置信区间，3.91 至 5.65；风险比 [HR]，0.80 [95% 置信区间，0.66 至 0.97]；P = .022）。

One-year OS was 27.3% versus 16.9%.

一年总生存率为27.3%对比16.9%。

Median progression-free survivalwas similar: 2.04 months (95% CI, 2.00 to 2.10) with ultra-low-dose nivolumab and 2.09 months (95% CI, 2.04 to 2.17) with chemotherapy (HR, 1.03 [95% CI, 0.86 to 1.23]; P = .77).

中位无进展生存期相似：超低剂量纳武利尤单抗治疗组为2.04个月（95%置信区间，2.00至2.10个月），化疗组为2.09个月（95%置信区间，2.04至2.17个月）（风险比，1.03 [95%置信区间，0.86至1.23]；P = .77）。

Grade ≥3 treatment-related adverse events were less frequent with ultra-low-dose nivolumab (42.5% v 60.8%; P < .001).

与超低剂量纳武利尤单抗相比，3级或更高级别的治疗相关不良事件发生率较低（42.5%对比60.8%；P<.001）。

Quality of life (QoL) was significantly better with ultra-low-dose nivolumab.

超低剂量纳武利尤单抗治疗下的生活质量（QoL）显著更好。

Conclusions

Ultra-low-dose nivolumab significantly improves OS versus chemotherapy in pretreated solid tumors, with fewer severe toxicities and better QoL.

超低剂量的纳武利尤单抗在预处理的实体瘤患者中显著改善总生存期，与化疗相比，严重毒性的发生率更低，生活质量更好。

These findings support re-evaluation of ICI dosing strategies and may enhance global access.

这些发现支持重新评估ICI（免疫检查点抑制剂）的剂量策略，并可能提高全球的可及性。