Real-World Outcomes in Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer in Argentina: A Multicenter Retrospective Study (GAOT-ALK001).

Abstract

In Argentina, anaplastic lymphoma kinase (ALK) gene rearrangements occur in approximately 6.1% of non-small cell lung cancer (NSCLC) cases. Given the availability of second- and third-generation ALK inhibitors, real-world data are needed to inform optimal treatment strategies. However, access to these therapies remains limited for many patients. We conducted a multicenter retrospective study of patients with metastatic ALK-positive NSCLC (ALKp) treated with first-line tyrosine kinase inhibitors (TKIs) from January 2014 to February 2024. Demographics, treatment patterns, clinical outcomes, and factors affecting treatment accessibility were analyzed. We identified 104 patients with ALKp. The median age was 55 years (IQR, 45-67); 86% had Eastern Cooperative Oncology Group ≤1, 58% were women, and 57% were nonsmokers. Brain metastases were present at diagnosis in 29%, with 50% receiving local treatment. First-line TKIs included alectinib (42%), crizotinib (30%), lorlatinib (16%), and brigatinib (12%). Crizotinib use was frequently due to limited access to new-generation TKIs. Adverse events occurred in 54%, with 21% grade 3 to 4. The objective response rate was 73%. At a median follow-up of 42 months, 48% experienced progression. Crizotinib was associated with higher risk of progression or death compared with newer TKIs (hazard ratio, 3.09 [95% CI, 1.75 to 5.5]; <i>P</i> = .01). CNS progression occurred in 18%, more often with crizotinib (42% <i>v</i> 8%, <i>P</i> = .04). Among those progressing, 82% received second-line therapy, most commonly lorlatinib or alectinib. The overall survival at 24 months was 81%, with 27% of patients deceased at data cutoff. This real-world study describes outcomes and treatment patterns among patients with ALKp in Argentina. It highlights disparities in access to optimal therapies and reinforces the need for equitable access to new-generation ALK inhibitors to improve clinical outcomes.