Transl Lung Cancer Res. 2025 Jun 30;14(6):2197-2209. doi: 10.21037/tlcr-2025-505. Epub 2025 Jun 26.
ABSTRACT
BACKGROUND: Treatment of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (ALK) 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.
METHODS: We retrospectively collected the data of advanced NSCLC patients with ALK-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.
RESULTS: 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 vs. 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 vs. without immunotherapy: 1.5 vs. 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).
CONCLUSIONS: 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.
PMID:40673075 | PMC:PMC12261234 | DOI:10.21037/tlcr-2025-505
