Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous NSCLC That Responded to First-Line Pembrolizumab Plus Chemotherapy.

Methods

In this randomized, double-blind, phase 3 trial (NCT03976362), adults with previously untreated stage IV squamous NSCLC received four cycles of induction therapy (pembrolizumab 200 mg every 3 weeks plus carboplatin and paclitaxel or nab-paclitaxel).

在这项随机、双盲、III期试验（NCT03976362）中，先前未经治疗的IV期鳞状非小细胞肺癌成人患者接受了四周期诱导治疗（每3周给予200 mg帕博利珠单抗，联合卡铂和紫杉醇或白蛋白结合紫杉醇）。

Patients with disease control were randomized to 31 cycles of pembrolizumab 200 mg every 3 weeks plus olaparib 300 mg orally twice daily or placebo.

疾病得到控制的患者被随机分配接受每3周200毫克的帕博利珠单抗治疗31个周期，同时每天两次口服300毫克的奥拉帕利或安慰剂。

Dual primary end points were progression-free survival(PFS) and overall survival(OS).

双重主要终点是无进展生存期（PFS）和总生存期（OS）。

PFS was tested at interim analysis 2 (the final PFS analysis); OS was tested at final analysis.

无进展生存期（PFS）在中期分析2（即最终PFS分析）中进行了测试；总生存期（OS）在最终分析中进行了测试。

Results

A total of 851 patients received induction treatment; 296 were randomized to pembrolizumab plus olaparib and 295 to pembrolizumab plus placebo.

共有851名患者接受了诱导治疗；其中296名被随机分配到帕博利珠单抗联合奥拉帕利组，295名被随机分配到帕博利珠单抗联合安慰剂组。

At interim analysis 2, with median follow-up of 27.1 months, median (95% confidence interval[CI]) PFS was 8.3 (6.7‒9.7) months in the pembrolizumab plus olaparib group and 5.4 (4.1‒5.6) months in the pembrolizumab plus placebo group (hazard ratio= 0.77, 95% CI: 0.63‒0.93, p = 0.0040 [not significant at a one-sided superiority boundary of p = 0.003]).

在中期分析2中，中位随访时间为27.1个月，pembrolizumab联合olaparib组的无进展生存期（PFS）中位数为8.3个月（95%置信区间[CI]：6.7‒9.7个月），而pembrolizumab联合安慰剂组的PFS中位数为5.4个月（95% CI：4.1‒5.6个月）（风险比=0.77，95% CI：0.63‒0.93，p = 0.0040 [在单侧优越性边界p = 0.003时不显著]）。

At final analysis, with median follow-up of 33.4 months, median (95% CI) OS was 19.1 (15.9‒22.2) and 18.6 (16.0‒21.6) months, respectively (hazard ratio= 1.01, 95% CI: 0.83‒1.24, p = 0.5481).

在最终分析中，中位随访时间为33.4个月，总生存期（OS）的中位数分别为19.1个月（95% CI：15.9‒22.2个月）和18.6个月（95% CI：16.0‒21.6个月）（风险比=1.01，95% CI：0.83‒1.24，p = 0.5481）。

Treatment-related adverse events occurred in 76.5% and 65.1% of patients, respectively.

分别有76.5%和65.1%的患者出现了与治疗相关的不良事件。

Conclusions

Adding olaparib to pembrolizumab as maintenance therapy for metastatic squamous NSCLC did not significantly improve PFS versus pembrolizumab plus placebo; neither PFS nor OS met the prespecified statistical significance boundary.

将奥拉帕利添加到帕博利珠单抗作为转移性鳞状非小细胞肺癌的维持治疗，并没有显著改善无进展生存期（PFS）与帕博利珠单抗加安慰剂相比；无进展生存期（PFS）和总生存期（OS）均未达到预先设定的统计显著性界限。

No new safety signals were identified.

未发现新的安全信号。

trial_registration

ClinicalTrials.gov, NCT03976362.

临床试验注册：ClinicalTrials.gov, NCT03976362。