WCLC 2025 - Posters & ePosters-EP.12.57 Ensartinib Exhibits Potential Synergistic Effects With Radiotherapy in ALK-Positive Non-Small Cell Lung Cancer

EP.12.57 Ensartinib Exhibits Potential Synergistic Effects With Radiotherapy in ALK-Positive Non-Small Cell Lung Cancer

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This study investigates the potential synergistic effects of ensartinib, an ALK inhibitor, combined with radiotherapy in treating ALK-positive non-small cell lung cancer (NSCLC). Ensartinib has shown clinical benefit in such patients, while radiotherapy remains a key local treatment modality. However, the efficacy of combining these two treatments had not been previously established.<br /><br />Clinical data from a phase II trial (NCT03215693) and in vitro experiments using ALK-positive H3122 cells harboring the EML4-ALK fusion mutation were analyzed. The clinical cohort consisted of 97 advanced NSCLC patients who experienced disease progression on crizotinib, with 38.1% having received prior brain radiotherapy. Key endpoints included progression-free survival (PFS), overall survival (OS), and safety.<br /><br />Results indicated no statistically significant difference in median PFS or OS between patients with or without prior brain radiotherapy, although a trend toward longer PFS was observed in the irradiated group. Neurological treatment-emergent adverse events occurred at similar rates (~29%) regardless of prior radiotherapy, suggesting tolerable safety profiles for the combination.<br /><br />In vitro assays demonstrated enhanced anti-tumor activity when ensartinib was combined with radiotherapy compared to either treatment alone, supporting potential synergy at the cellular level.<br /><br />The authors conclude that both clinical and preclinical data suggest a promising synergistic effect between ensartinib and radiotherapy in ALK-positive NSCLC. However, they emphasize the preliminary nature of this exploratory analysis and highlight the need for further clinical trials to validate these findings and better define optimal treatment strategies combining ALK inhibitors and radiotherapy.<br /><br />In summary, combining ensartinib with radiotherapy may improve outcomes in ALK-positive NSCLC, particularly in patients with brain metastases, warranting additional investigation.

Asset Subtitle

Buhai Wang

Meta Tag

Speaker Buhai Wang

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

ensartinib

ALK inhibitor

radiotherapy

ALK-positive

non-small cell lung cancer

NSCLC

EML4-ALK fusion

progression-free survival

brain metastases

combination therapy