Lazertinib Versus Osimertinib in Previously Untreated EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind, Exploratory Analysis From MARIPOSA.

In the phase 3 MARIPOSA study, amivantamab plus lazertinib (amivantamab-lazertinib) significantly improved progression-free survival(PFS; p < 0.001) versus osimertinib in participants with treatment-naive EGFR-mutant advanced NSCLC.

在第三阶段MARIPOSA研究中，与osimertinib相比，amivantamab联合lazertinib（amivantamab-lazertinib）显著改善了无进展生存期（PFS；p < 0.001），在未接受过治疗的EGFR突变型晚期NSCLC患者中。

A lazertinib monotherapy arm was included to assess the contribution of components in the combination.

纳入了 lazertinib 单药治疗组以评估联合治疗中各成分的贡献。

This is the first randomized, double-blindcomparison of two third-generation EGFR TKIs, lazertinib and osimertinib.

这是首次对两种第三代EGFR酪氨酸激酶抑制剂 lazertinib 和 osimertinib 进行的随机、双盲比较。

Methods

In MARIPOSA, 1074 participants were randomized 2:2:1 to receive amivantamab-lazertinib (n = 429), osimertinib monotherapy (n = 429), or lazertinib monotherapy (n = 216).

在MARIPOSA研究中，共有1074名参与者按2:2:1的比例随机分配接受amivantamab-lazertinib（n = 429）、osimertinib单药治疗（n = 429）或lazertinib单药治疗（n = 216）。

This exploratory analysis compared the efficacy and safety of lazertinib and osimertinib.

这项探索性分析比较了lazertinib和osimertinib的疗效和安全性。

Results

At a median follow-up of 22.0 months, median PFS was 18.5 months for lazertinib versus 16.6 months for osimertinib (hazard ratio= 0.98, 95% confidence interval: 0.79-1.22; p = 0.86).

在中位随访22.0个月时，lazertinib的中位无进展生存期（PFS）为18.5个月，而osimertinib为16.6个月（风险比=0.98，95%置信区间：0.79-1.22；p=0.86）。

PFS results were comparable between arms among predefined subgroups.

在预定义的亚组中，两组的PFS结果相当。

Among participants with measurable disease at baseline, objective response ratewas 83% for lazertinib versus 85% for osimertinib, with a median duration of response among confirmed responders of 16.6 months versus 16.8 months, respectively.

在基线时具有可测量疾病的参与者中，lazertinib的客观缓解率为83%，而osimertinib为85%，在确认为缓解的患者中，中位缓解持续时间分别为16.6个月和16.8个月。

Median overall survivalwas not reached for both arms (hazard ratio= 1.00, 95% confidence interval: 0.73-1.38) at the interim analysis.

在中期分析时，两组的中位总生存期均未达到（风险比=1.00，95%置信区间：0.73-1.38）。

Adverse events for both arms were mostly grades 1 to 2 and frequently related to EGFR inhibition.

两组的不良事件大多为1至2级，并且通常与表皮生长因子受体（EGFR）抑制有关。

Lazertinib was associated with lower rates of QT interval prolongation versus osimertinib.

与奥希替尼相比，拉泽替尼与较低的QT间期延长发生率相关。

Conclusions

Lazertinib demonstrated comparable efficacy and safety to osimertinib, including in predefined subgroups.

Lazertinib展示了与osimertinib相当的疗效和安全性，包括在预定义的亚组中。