Tian Guangming, Nie Jun, Dai Ling, Hu Weiheng, Zhang Jie, Wu Di, Ma Xiangjuan, Chen Xiaoling, Han Sen, Han Jindi, Zhang Ziran, Long Jieran, Zhao Xinliang, Fang Jian
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Thoracic Oncology Department II, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Medical Genetics, School of Basic Sciences, Peking University, Beijing, China.
Front Oncol. 2025 May 1;15:1577607. doi: 10.3389/fonc.2025.1577607. eCollection 2025.
Lorlatinib, a third-generation ALK inhibitor, has demonstrated strong efficacy in treating advanced ALK-positive NSCLC, though real-world data, particularly from China, are limited. This study evaluates the real-world efficacy and safety of lorlatinib in Chinese patients with advanced ALK-positive NSCLC.
This retrospective study analyzed 65 patients with advanced ALK-positive NSCLC who received lorlatinib at Peking University Cancer Hospital between September 2017 and August 2024. The study assessed the overall response rate (ORR), progression-free survival (PFS), and safety outcomes, comparing first-line treatment to subsequent treatments after prior ALK inhibitor exposure.
The real-world ORR (rwORR) for all patients was 49.2%, with a real-world disease control rate (rwDCR) of 92.3%. In the first-line treatment group (n=8), lorlatinib showed an ORR of 100%, and no patients experienced progressive disease (PD) during a median follow-up of 9 months. The mPFS for the entire cohort was 37.83 months, with the median OS (mOS) not reached (NR, 95% CI: NR-NR). Patients who had received one prior ALK inhibitor had a mPFS of 49.73 months, while those who had received two or more prior ALK inhibitors had a mPFS of 12.17 months. A statistically significant difference in mOS was found between patients with one prior ALKi and those with two or more prior ALKis (p = 0.032). Lorlatinib demonstrated strong intracranial efficacy, with a 45.2% intracranial ORR in patients with brain metastases. The safety profile was consistent with previous reports, with the most common AEs being hyperlipidemia. However, the incidence of severe AEs was manageable with dose adjustments and supportive treatments.
Lorlatinib demonstrates strong efficacy and manageable safety, especially in first-line treatment of advanced ALK-positive NSCLC, supporting its role as an effective treatment option.
洛拉替尼是一种第三代ALK抑制剂，在治疗晚期ALK阳性非小细胞肺癌（NSCLC）方面已显示出强大疗效，不过真实世界数据，尤其是来自中国的数据有限。本研究评估了洛拉替尼在中国晚期ALK阳性NSCLC患者中的真实世界疗效和安全性。
这项回顾性研究分析了2017年9月至2024年8月期间在北京大学肿瘤医院接受洛拉替尼治疗的65例晚期ALK阳性NSCLC患者。该研究评估了总缓解率（ORR）、无进展生存期（PFS）和安全性结果，比较了一线治疗与先前接受ALK抑制剂治疗后的后续治疗情况。
所有患者的真实世界总缓解率（rwORR）为49.2%，真实世界疾病控制率（rwDCR）为92.3%。在一线治疗组（n = 8）中，洛拉替尼的ORR为100%，在9个月的中位随访期间，无患者出现疾病进展（PD）。整个队列的中位PFS为37.83个月，中位总生存期（mOS）未达到（NR，95%CI：NR - NR）。接受过一种先前ALK抑制剂治疗的患者中位PFS为49.73个月，而接受过两种或更多种先前ALK抑制剂治疗的患者中位PFS为12.17个月。在接受过一种先前ALK抑制剂治疗的患者与接受过两种或更多种先前ALK抑制剂治疗的患者之间，mOS存在统计学显著差异（p = 0.032）。洛拉替尼显示出强大的颅内疗效，脑转移患者的颅内ORR为45.2%。安全性概况与先前报告一致，最常见的不良事件是高脂血症。然而，通过剂量调整和支持性治疗，严重不良事件的发生率是可控的。
洛拉替尼显示出强大的疗效和可控的安全性，尤其是在晚期ALK阳性NSCLC的一线治疗中，支持其作为一种有效治疗选择的作用。
