Efficacy of targeted therapy in lung cancer with rare ALK fusions

Abstract Paradigms about anaplastic lymphoma kinase (ALK)-driven non-small cell lung cancer (NSCLC) have been shaped by EML4::ALK. There is little evidence on the remaining patients, presenting with a plethora of other fusion partners (rare ALK). We compared real-world data of patients with advanced NSCLC and rare ALK fusions to patients with EML4::ALK fusions. Patients with rare ALK fusions (n = 51) were older and more likely to have a history of smoking. Overall survival (OS) tended to be shorter. Tyrosine kinase inhibitors (TKI) were used less and chemotherapies more frequently as first-line palliative treatment. Patients with rare ALK fusions had a significantly shorter progression-free survival (PFS) when treated with first-line platinum-based chemotherapy as opposed to TKI. There was, however, no PFS difference between rare ALK and EML4::ALK positive patients receiving TKI as first-line treatment. Taken together, patients with advanced NSCLC harboring rare ALK fusions derive comparable benefit from TKI as patients with EML4::ALK.