The Phase 3 KEYLYNK-006 Study of Pembrolizumab Plus Olaparib Versus Pembrolizumab Plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous NSCLC.

Methods

In the phase 3 KEYLYNK-006 trial (NCT03976323), eligible adults with previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations who had complete response, partial response, or stable disease after induction therapy with four cycles of pembrolizumab 200 mg every three weeks, pemetrexed 500 mg/m2, and carboplatin area under the concentration-time curve 5 mg/mL/min or cisplatin 75 mg/m2 were randomized in a one-to-one ratio to olaparib 300 mg orally twice daily or pemetrexed every three weeks, both given with up to 31 cycles of pembrolizumab every three weeks.

在第三阶段KEYLYNK-006试验（NCT03976323）中，符合条件的成年人患有先前未经治疗的转移性非鳞状非小细胞肺癌，没有可靶向的遗传改变，在接受四周期的pembrolizumab 200 mg每三周一次、pemetrexed 500 mg/m2和carboplatin浓度-时间曲线下面积5 mg/mL/min或顺铂75 mg/m2的诱导治疗后，完全缓解、部分缓解或疾病稳定，被随机分为1:1比例，分别口服奥拉帕利300 mg每日两次或每三周一次的pemetrexed，两者均与最多31个周期的每三周一次的pembrolizumab联合使用。

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

主要终点是无进展生存期（PFS）和总生存期（OS）。

Progression-free survivalwas tested at interim analysis 2 (i.e., final PFS analysis) and OS at final analysis (FA).

无进展生存期在中期分析2（即最终PFS分析）进行测试，总生存期在最终分析（FA）进行测试。

Results

Of 1003 patients who received induction therapy, 672 (67.0%) were randomized to pembrolizumab plus olaparib (n = 337) or pembrolizumab plus pemetrexed (n = 335) in the intention-to-treatpopulation.

在接受诱导治疗的1003名患者中，有672名（67.0%）被随机分配到意向治疗人群中的pembrolizumab联合olaparib组（n=337）或pembrolizumab联合pemetrexed组（n=335）。

Median follow-up at FA was 39.9 (range: 28.1-51.5) months.

在FA时的中位随访时间为39.9个月（范围：28.1-51.5个月）。

At interim analysis 2, the median (95% confidence interval[CI]) PFS was 7.1 (5.6-8.7) months versus 8.3 (6.9-11.5) months in the olaparib versus pemetrexed groups (hazard ratio= 1.12, 95% CI: 0.92-1.36, p = 0.87).

在中期分析2中，奥拉帕利组与培美曲塞组的无进展生存期（PFS）中位数（95%置信区间[CI]）分别为7.1（5.6-8.7）个月和8.3（6.9-11.5）个月（风险比=1.12，95% CI: 0.92-1.36，p = 0.87）。

At FA, the median (95% CI) OS was 20.7 (18.0-24.8) months versus 23.0 (19.0-26.4) months (hazard ratio= 1.04, 95% CI: 0.87-1.25, p = 0.6649).

在FA分析中，奥拉帕利组与培美曲塞组的总生存期（OS）中位数（95%置信区间[CI]）分别为20.7（18.0-24.8）个月和23.0（19.0-26.4）个月（风险比=1.04，95% CI: 0.87-1.25，p = 0.6649）。

Grade 3 to 5 maintenance treatment-related adverse events occurred in 26.1% versus 30.1% of patients, respectively.

3至5级维持治疗相关不良事件的发生率分别为26.1%和30.1%。

Conclusions

Pembrolizumab plus maintenance olaparib did not improve PFS or OS versus pembrolizumab plus pemetrexed in previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations.

Pembrolizumab联合维持Olaparib并未改善无靶向基因改变的初治转移性非鳞状非小细胞肺癌患者的无进展生存期或总生存期，与Pembrolizumab联合培美曲塞相比。