ArticleOncology and therapy2025
A Decade of Treating ALK-Rearranged Non-Small Cell Lung Cancer in a Lower Middle-Income Country: Changing Patterns and Improving Survival.
Article in Oncology and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionData regarding the comparative efficacy of various generations of tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC) in lower middle-income countries (LMICs) is scarce.
methodsA comprehensive assessment of anaplastic lymphoma kinase (ALK)-directed TKIs and treatment sequences was done for 249 patients (145 male, 104 female) with advanced NSCLC at a referral cancer hospital in New Delhi, India. The primary endpoints were overall survival (OS); progression-free survival on 1st-line (PFS1) therapy, 2nd-line (PFS2) therapy, and PFS1 + 2. Multivariable Cox proportional hazards and joint frailty modelling were used for progression events and OS, respectively.
resultsWith a median follow-up of 48 months, median OS, PFS1, and PFS1 + 2 were 46.6 (95% CI 36.9-67.0), 18.2 (95% CI 14.5-26.8), and 33.1 months (95% CI 28.6-41.6), respectively. Third-generation TKIs significantly improved PFS and OS over 1st-generation TKIs, whether used 1st-line or later (HR PFS1 0.08, 95% CI 0.02-0.32, p < 0.001; HR OS 0.13, 95% CI 0.02-0.94, p = 0.043; HR PFS2 0.36, 95% CI 0.19-0.71, p = 0.003). Joint frailty modelling confirmed the correlation between repeated progression events and mortality (shared frailty parameter theta = 1.78, p < 0.001). Alectinib (HR 0.53, 95% CI 0.33-0.84, p = 0.007) and lorlatinib (HR 0.49, 95% CI 0.31-0.77, p = 0.002) reduced progression risk. Temporal trend analyses showed fewer treatment lines and significantly improved outcomes in patients with brain metastases with 3rd-generation TKIs.
conclusionsThis relatively large LMIC real-world study shows similar outcomes to Western data, and improved survival and lower risk of intracranial progression with 2nd- and 3rd-generation ALK-directed TKIs.
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