2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.04 Clinical Outcomes of ALK Tyrosine Kinase Inhibitor Therapy in Patients with ALK Testing Discordance by Immunohistochemistry and Next-Generation Sequencing

PP01.04 Clinical Outcomes of ALK Tyrosine Kinase Inhibitor Therapy in Patients with ALK Testing Discordance by Immunohistochemistry and Next-Generation Sequencing

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This study examines the clinical outcomes of using ALK tyrosine kinase inhibitors (TKIs) in lung cancer patients with discordant ALK test results from immunohistochemistry (IHC) and next-generation sequencing (NGS). ALK fusions, often indicative of certain lung cancers, were analyzed using these two methods. While high concordance was typically observed between IHC and NGS, some discrepancies were noted, particularly in non-common ALK fusions.<br /><br />Eligible patients underwent NGS testing via MSK-IMPACT DNA-based hybrid capture or RNA-based anchored multiplex PCR to detect ALK fusions, while ALK expression was determined using IHC. The study reviewed 336 ALK-positive samples, majority diagnosed using either NGS or IHC. Patients with metastatic diseases primarily received first-line ALK TKI treatment.<br /><br />Key findings indicated that despite discordant ALK test results (either IHC-negative/NGS-positive or equivocal IHC/NGS-positive), patients still achieved durable disease control, suggesting potential benefits from ALK TKIs regardless of testing discrepancies. Specifically, patients with discordant results showed a surprisingly longer median progression-free survival than concordant cases, with median values observed at 39 and 41 months in IHCe/NGS and IHC-/NGS groups, respectively, compared to 26 months in concordant cases.<br /><br />The study also identified 16 non-EML4-ALK fusions, including 4 novel variants, underscoring the need for further exploration into these rare fusion types. This suggests the presence of undetected functional ALK fusions or other underlying mechanisms that contribute to treatment efficacy. The findings emphasize the necessity for continued research to better understand the clinical implications of ALK fusion detection methodologies and their impact on therapeutic decisions.

Asset Subtitle

Charles Hsu

Keywords

ALK tyrosine kinase inhibitors

lung cancer

discordant ALK test results

immunohistochemistry

next-generation sequencing

ALK fusions

progression-free survival

non-EML4-ALK fusions

treatment efficacy

clinical implications