Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 LEAP-006 Study.

Methods

Adults with previously untreated stage IV nonsquamous NSCLC without targetable genetic alterations were randomized 1:1 to lenvatinib 8 mg/d or placebo once daily plus pembrolizumab 200 mg every 3 weeks with pemetrexed and carboplatin or cisplatin for 4 cycles, followed by pembrolizumab (≤35 total cycles) and pemetrexed until disease progression or intolerable toxicity.

之前未经治疗的IV期非鳞状非小细胞肺癌（NSCLC）成人患者，且没有可靶向的遗传改变，被随机分为1:1两组，一组接受lenvatinib 8 mg/天或安慰剂每日一次，联合每3周一次的pembrolizumab 200 mg，以及pemetrexed和卡铂或顺铂化疗4个周期，随后使用pembrolizumab（最多35个周期）和pemetrexed，直至疾病进展或出现无法耐受的毒性。

Primary end points were progression-free survivaland overall survival(OS).

主要终点是无进展生存期和总生存期（OS）。

Part 1 was an open-label safety run-in of lenvatinib plus pembrolizumab and chemotherapy; part 2 was the randomized, double-blindstudy.

第一部分是对仑伐替尼联合派姆单抗和化疗的开放标签安全性研究；第二部分是随机、双盲研究。

Results

Participants (n = 748) were randomized to the lenvatinib (n = 375) or placebo (n = 373) arms.

参与者（n = 748）被随机分配到仑伐替尼（n = 375）或安慰剂（n = 373）组。

Median follow-up at final analysis (August 11, 2023) for OS was 36.8 months.

最终分析（2023年8月11日）时的总生存期中位随访时间为36.8个月。

Median (95% confidence interval[CI]) progression-free survivalwas 12.1 (10.4-14.1) versus 9.5 (8.3-10.7) months in the lenvatinib and placebo arms, respectively (hazard ratio, 0.88 [95% CI, 0.74-1.05]; 1-sided p = 0.07976).

无进展生存期的中位数（95%置信区间[CI]）在仑伐替尼组和安慰剂组分别为12.1（10.4-14.1）个月和9.5（8.3-10.7）个月（风险比，0.88 [95% CI, 0.74-1.05]；单侧p值=0.07976）。

Median (95% CI) OS was 21.8 (18.6-24.0) versus 22.1 (19.7-24.2) months (hazard ratio, 1.05 [95% CI, 0.88-1.26]; 1-sided p = 0.70818).

总生存期的中位数（95%置信区间[CI]）在仑伐替尼组和安慰剂组分别为21.8（18.6-24.0）个月和22.1（19.7-24.2）个月（风险比，1.05 [95% CI, 0.88-1.26]；单侧p值=0.70818）。

Grade 3 or higher treatment-related adverse events occurred in 69.7% and 55.6% of participants, respectively (grade 5, 5.6% versus 2.7%).

分别有69.7%和55.6%的参与者出现了3级或更高级别的治疗相关不良事件（5级，分别为5.6%和2.7%）

Conclusions

Adding lenvatinib to first-line pembrolizumab plus chemotherapy did not improve efficacy versus pembrolizumab plus chemotherapy in stage IV nonsquamous NSCLC without targetable genetic alterations.

在没有可靶向遗传改变的IV期非鳞状非小细胞肺癌中，将仑伐替尼加入到一线帕博利珠单抗加化疗中，并没有提高疗效，与仅使用帕博利珠单抗加化疗相比。

There were no new safety signals.

未发现新的安全信号。

Pembrolizumab plus chemotherapy remains a standard of care for this population.

帕博利珠单抗联合化疗仍然是这一人群的标准治疗方案。

trial_registration

ClinicalTrials.gov (https://clinicaltrials.gov/), NCT03829319.

临床试验注册中心 (https://clinicaltrials.gov/), NCT03829319。