Wang Danni, Li Yujing, Liu Beibei, Lou Yuqing, Zhang Lele, Sun Yueran, Qian Fangfei, Lu Jun, Li Fusheng, Urbanska Edyta M, Kauffmann-Guerrero Diego, Wu Xinwei, Han Baohui, Zhang Yanwei, Zhang Wei
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
High School Affiliated to Shanghai Jiao Tong University, Shanghai, China.
Transl Lung Cancer Res. 2025 Jun 30;14(6):2197-2209. doi: 10.21037/tlcr-2025-505. Epub 2025 Jun 26.
Treatment of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase () rearranged non-small cell lung cancer (NSCLC) remains an unmet need. Among these patients, the efficacy of immunotherapy has not been thoroughly investigated. The purpose of our study was to evaluate the efficacy of immunotherapy in patients with ALK-TKI-resistant NSCLC, stratified by programmed cell death ligand-1 (PD-L1) expression.
We retrospectively collected the data of advanced NSCLC patients with -rearrangement, who were treated with immunotherapy or chemotherapy after the development of ALK-TKI resistance at the Shanghai Chest Hospital. Progression-free survival (PFS) was used to evaluate the outcomes.
The final analysis included 89 patients between June 1, 2018, and December 31, 2022, who met the selection criteria. The entire cohort had a median follow-up time of 33.4 months. The patients who received immunotherapy had better PFS than those who received non-immunotherapy (median PFS: 5.3 2.5 months; P=0.009). The PD-L1-positive patients who received immunotherapy had a median PFS of 7.1 months, while those who received non-immunotherapy had a median PFS of 2.5 months (P=0.02). No such statistically significant difference was observed in the PD-L1-negative patients (median PFS for with immunotherapy without immunotherapy: 1.5 2.9 months; P=0.68). The PD-L1-positive patients who underwent re-biopsy after the development of TKI resistance and who received immunotherapy had a PFS of 7.8 months, while those who received non-immunotherapy had a PFS of 2.7 months (P=0.002).
This was the first real-world retrospective study to show that some patients with positive PD-L1 expression may benefit from immune-based therapy after the development of ALK-TKI resistance. However, we still recommend biopsy for patients who develop ALK-TKI resistance to provide further treatment guidance.
酪氨酸激酶抑制剂（TKI）耐药的间变性淋巴瘤激酶（ALK）重排非小细胞肺癌（NSCLC）的治疗仍存在未满足的需求。在这些患者中，免疫疗法的疗效尚未得到充分研究。我们研究的目的是评估免疫疗法在ALK-TKI耐药NSCLC患者中的疗效，并根据程序性细胞死亡配体-1（PD-L1）表达进行分层。
我们回顾性收集了上海胸科医院中ALK重排的晚期NSCLC患者的数据，这些患者在出现ALK-TKI耐药后接受了免疫疗法或化疗。采用无进展生存期（PFS）来评估疗效。
最终分析纳入了2018年6月1日至2022年12月31日期间符合入选标准的89例患者。整个队列的中位随访时间为33.4个月。接受免疫疗法的患者的PFS优于接受非免疫疗法的患者（中位PFS：5.3对2.5个月；P=0.009）。接受免疫疗法的PD-L1阳性患者的中位PFS为7.1个月，而接受非免疫疗法的患者的中位PFS为2.5个月（P=0.02）。在PD-L1阴性患者中未观察到这种统计学上的显著差异（接受免疫疗法与未接受免疫疗法的中位PFS：1.5对2.9个月；P=0.68）。TKI耐药后接受重新活检并接受免疫疗法的PD-L1阳性患者的PFS为7.8个月，而接受非免疫疗法的患者的PFS为2.7个月（P=0.002）。
这是第一项真实世界的回顾性研究，表明一些PD-L1表达阳性的患者在ALK-TKI耐药后可能从免疫治疗中获益。然而，我们仍然建议对出现ALK-TKI耐药的患者进行活检，以提供进一步的治疗指导。
