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

Abstract

Purpose: 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.

Methods: 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.

Results: 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]; P = .01). CNS progression occurred in 18%, more often with crizotinib (42% v 8%, P = .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.

Conclusion: 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.