WCLC 2025 - Posters & ePosters-P3.12.28 Association of PD-L1 Expression With Clinical Outcome in Advanced NSCLC With ALK Rearrangement

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This retrospective study from Ramathibodi Hospital, Thailand, evaluates the relationship between PD-L1 expression and clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients harboring ALK rearrangements treated primarily with ALK tyrosine kinase inhibitors (ALK-TKIs). Among 87 predominantly female, never-smoking patients (median age 65), PD-L1 positivity (tumor proportion score ≥1%) was high at 77%, with strong expression (TPS ≥50%) in 30%. PD-L1-positive patients more frequently presented with brain metastases.<br /><br />First-line ALK-TKI therapy was administered to 75% of patients, mostly with first-generation (crizotinib) or second-generation (ceritinib) inhibitors, showing significantly longer progression-free survival (PFS) than chemotherapy (median PFS 22 vs. 4 months; HR 0.24; p<0.001). Notably, second- or third-generation ALK-TKIs conferred better 5-year PFS (38.5%). Multiple ALK-TKI treatment lines correlated with prolonged chemotherapy-free survival (5.1 vs. 2.9 years) and trended toward improved overall survival (OS). Intracranial progression was more common among PD-L1-negative patients, suggesting superior CNS control with ALK-TKIs.<br /><br />Although PD-L1 positivity was associated with a non-significant trend toward poorer PFS (HR 1.21) and OS (HR 1.68), the data did not achieve statistical significance. Univariate analyses indicated factors such as male gender, smoking, and presence of metastases worsened OS, while multiple ALK-TKI lines showed a survival benefit trend. Multivariate analysis confirmed first-line treatment with later-generation ALK-TKIs significantly improved PFS.<br /><br />This real-world Thai cohort reveals a high PD-L1 co-expression rate in ALK-positive NSCLC, with PD-L1 positivity possibly linked to worse prognosis, though further validation is needed. The study supports the superior efficacy of later-generation ALK-TKIs in PFS and CNS metastasis control and suggests administering multiple ALK-TKI lines may improve survival while delaying chemotherapy. Limitations include retrospective design, small sample size, and limited access to newer ALK-TKIs due to reimbursement constraints.

Asset Subtitle

Nattanit Suriyaphan

Meta Tag

Speaker Nattanit Suriyaphan

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

PD-L1 expression

ALK rearrangements

non-small cell lung cancer

ALK tyrosine kinase inhibitors

progression-free survival

brain metastases

crizotinib

ceritinib

intracranial progression

overall survival