Alectinib versus crizotinib in previously untreated ALK-positive advanced non-small cell lung cancer: final overall survival analysis of the phase III ALEX study.

This final analysis provides mature overall survival(OS), duration of response (DOR) and long-term safety data.

本次最终分析提供了成熟的总生存（OS）、反应持续时间（DOR）和长期安全性数据。

patients_and_methods

Treatment-naïve patients with stage III/IV ALK-positive NSCLC were randomly assigned to receive alectinib [600 mg twice daily (b.i.d.)] or crizotinib (250 mg b.i.d.) until disease progression, unacceptable toxicity, withdrawal, or death.

治疗前的III/IV期ALK阳性非小细胞肺癌患者被随机分配接受阿来替尼[每日两次，每次600毫克（b.i.d.）]或克唑替尼[每日两次，每次250毫克（b.i.d.）]，直至疾病进展、不可接受的毒性、撤回或死亡。

Primary endpoint was investigator-assessed progression-free survival(previously reported).

主要终点是研究者评估的无进展生存期（先前已报告）。

Key secondary endpoints included OS, DOR and safety.

主要次要终点包括总生存期(OS)、缓解持续时间(DOR)和安全性。

Results

A total of 303 patients (alectinib, n = 152; crizotinib, n = 151) were enrolled.

共有303名患者（阿来替尼组，n=152；克唑替尼组，n=151）被纳入研究。

At the updated data cut-off (28 April 2025), after a median follow-up of 53.5 (alectinib) and 23.3 (crizotinib) months, median OS was 81.1 [95% confidence interval(CI) 62.3 months-not estimable] versus 54.2 (95% CI 34.6-75.6 months) months, respectively [hazard ratio(HR) 0.78; 95% CI 0.56-1.08].

在2025年4月28日的数据截止日期更新后，经过中位随访时间53.5个月（alectinib）和23.3个月（crizotinib），中位总生存期为81.1个月[95%置信区间（CI）62.3个月-不可估计]与54.2个月（95%置信区间34.6-75.6个月）（风险比[HR] 0.78; 95%置信区间0.56-1.08）。

Improvement in median OS was observed with alectinib in patients with and without central nervous system (CNS) metastases at baseline [with CNS metastases: 63.4 (n = 59) versus 30.9 (n = 53) months with alectinib versus crizotinib, respectively (HR 0.68; 95% CI 0.40-1.15); without CNS metastases: 94.0 (n = 93) versus 69.8 (n = 98) months (HR 0.87; 95% CI 0.58-1.32)].

在基线时有无中枢神经系统（CNS）转移的患者中，使用alectinib观察到中位总生存期的改善[有CNS转移：63.4个月（n = 59）与30.9个月（n = 53）使用alectinib与crizotinib相比（HR 0.68; 95%置信区间0.40-1.15）；无CNS转移：94.0个月（n = 93）与69.8个月（n = 98）（HR 0.87; 95%置信区间0.58-1.32）]。

Median DOR in confirmed responders was longer with alectinib (42.3 months, 95% CI 31.3-51.3 months) versus crizotinib [11.1 months, 95% CI 7.9-13.0 months (HR 0.41; 95% CI 0.30-0.56)].

在确认的应答者中，与克唑替尼相比，阿来替尼的中位反应持续时间更长（42.3个月，95%置信区间31.3-51.3个月），而克唑替尼为11.1个月，95%置信区间7.9-13.0个月（HR 0.41；95%置信区间0.30-0.56）。

Long-term safety (median duration of alectinib treatment, 28.1 months) remained consistent with earlier reports, with no new or unexpected safety concerns identified.

长期安全性（阿来替尼治疗的中位持续时间28.1个月）与早期报告一致，未发现新的或意外的安全问题。

Conclusions

These final OS data show the sustained long-term systemic and intracranial efficacy of alectinib in the first-line treatment of ALK-positive NSCLC and confirm alectinib as a standard of care in this setting.

这些最终的总生存数据显示了在ALK阳性非小细胞肺癌一线治疗中，阿来替尼的长期全身和颅内疗效持续存在，并确认阿来替尼作为此情况下的治疗标准。