Pembrolizumab With or Without Lenvatinib as First-Line Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Phase III LEAP-010 Study.

In LEAP-010 (ClinicalTrials.gov identifier: NCT04199104), the multikinase inhibitor lenvatinib plus pembrolizumab was evaluated as first-line therapy in participants with PD-L1 combined positive score (CPS) ≥1 R/M HNSCC.

在LEAP-010研究（ClinicalTrials.gov注册号：NCT04199104）中，多激酶抑制剂仑伐替尼联合帕博利珠单抗作为一线治疗方案，评估了PD-L1联合阳性评分（CPS）≥1的R/M HNSCC患者。

Methods

In this phase III, randomized, placebo-controlled, double-blindstudy, participants 18 years and older with PD-L1 CPS ≥1 R/M HNSCC deemed incurable by local therapy were randomly assigned 1:1 to lenvatinib 20 mg plus pembrolizumab 200 mg IV once every 3 weeks for ≤35 cycles or placebo orally once daily plus pembrolizumab 200 mg IV once every 3 weeks for ≤35 cycles.

在这项III期、随机、安慰剂对照、双盲研究中，年龄在18岁及以上的PD-L1 CPS ≥1的R/M HNSCC患者，被认为无法通过局部治疗治愈，被随机分配为1:1，接受每3周一次的lenvatinib 20 mg联合pembrolizumab 200 mg静脉注射，最多35个周期，或接受每日一次的安慰剂口服联合每3周一次的pembrolizumab 200 mg静脉注射，最多35个周期。

Primary end points were objective response rate(ORR), progression-free survival(PFS), and overall survival(OS).

主要终点是客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。

Per the prespecified analysis plan, ORR and PFS were reported from the first interim analysis (IA1; data cutoff: July 6, 2022), and OS from IA2 (data cutoff: May 30, 2023).

根据预先设定的分析计划，客观缓解率(ORR)和无进展生存期(PFS)是从第一次中期分析(IA1;数据截止日期:2022年7月6日)报告的，而总生存(OS)是从第二次中期分析(IA2;数据截止日期:2023年5月30日)报告的。

Results

Five hundred eleven participants were randomly assigned to lenvatinib plus pembrolizumab (n = 256) or placebo plus pembrolizumab (n = 255).

共有511名参与者被随机分配到仑伐替尼加派姆单抗组(n = 256)或安慰剂加派姆单抗组(n = 255)。

The median time from random assignment to data cutoff was 11.5 months for IA1 and 21.3 months for IA2.

从随机分组到数据截止的中位时间是11.5个月对于IA1和21.3个月对于IA2。

At IA1, the median PFS was 6.2 months for lenvatinib plus pembrolizumab versus 2.8 months for placebo plus pembrolizumab (hazard ratio[HR], 0.64 [95% CI, 0.50 to 0.81]; P = .0001040); the ORR was 46.1% versus 25.4%, respectively (difference = 20.2% [95% CI, 10.5 to 29.6]; P = .0000251).

在IA1，中位无进展生存期（PFS）为6.2个月，对于仑伐替尼联合派姆单抗，而对照组为2.8个月，对于安慰剂联合派姆单抗（风险比[HR]，0.64 [95% 置信区间，0.50至0.81]；P = .0001040）；客观缓解率（ORR）分别为46.1%和25.4%（差异为20.2% [95% 置信区间，10.5至29.6]；P = .0000251）。

At IA2, the median OS was 15.0 months for lenvatinib plus pembrolizumab versus 17.9 months for placebo plus pembrolizumab (HR,1.15 [95% CI, 0.91 to 1.45]; P = .882).

在IA2阶段，接受仑伐替尼联合派姆单抗治疗的患者的中位总生存期为15.0个月，而接受安慰剂联合派姆单抗治疗的患者的中位总生存期为17.9个月（风险比，1.15 [95% 置信区间，0.91至1.45]；P = .882）。

At IA2, 170 (66.9%) participants receiving lenvatinib plus pembrolizumab had grade 3-4 all-cause adverse events compared with 97 (38.3%) participants on placebo plus pembrolizumab.

在IA2阶段，接受仑伐替尼联合派姆单抗治疗的170名（66.9%）参与者出现了3-4级的全因不良事件，相比之下，接受安慰剂联合派姆单抗治疗的97名（38.3%）参与者出现了3-4级的全因不良事件。

Conclusions

In participants with PD-L1 CPS ≥1 R/M HNSCC, first-line lenvatinib plus pembrolizumab significantly improved ORR and PFS, but not OS, compared with placebo plus pembrolizumab.

在PD-L1 CPS ≥1的复发/转移性头颈部鳞状细胞癌患者中，一线使用仑伐替尼联合派姆单抗显著提高了客观缓解率和无进展生存期，但总生存期未见改善，与安慰剂联合派姆单抗相比。

The safety profile was consistent with published data.

安全性特征与已发表数据一致。