Lorlatinib in the second line and beyond for ALK positive lung cancer: real-world data from resource-constrained settings

Abstract

Abstract Background ALK-positive lung cancers are known to have favorable responses with oral tyrosine kinase inhibitors. Lorlatinib is an approved treatment option post first and second-line ALK inhibitors and is now also in first line. We present a retrospective observational study of the safety and efficacy of patients receiving Lorlatinib in second-line and beyond. Methods We conducted a retrospective observational study of ALK-positive patients who received Lorlatinib post-progression or intolerance to initial therapy at the Medical Oncology department. The patients who were started on Lorlatinib between January 2018 to December 2019 were included. The patients underwent routine blood and radiological evaluation every two to three months. Results A total of 38 patients received Lorlatinib in the specified period. The median age was 48 years (range 23–68), with 53% of patients being male, 37% having comorbidities; the most common being hypertension and diabetes and 79% of patients were of ECOG-PS1. Twenty-two patients (58%) had received two prior TKIs. The most common sites of metastasis before starting Lorlatinib were brain (55%) and bone (53%). All patients except one received prior whole-brain radiotherapy with 4 receiving radiation twice. The median follow-up period was 49 months (95% CI: 46.4–51.6). Eighty-four percent showed disease control with median progression-free survival (PFS) and overall survival (OS) of 16 months (95% CI 5.4–26.6) and 22 months (95% CI 9.9–34.1) respectively. Twelve patients died without documented progression. Five out of twelve with documented progression had brain involvement while six had lung involvement. Twelve out of twenty-four patients who progressed received subsequent chemotherapy. The most common grade 3 and above toxicities were hypercholesterolemia and hypertriglyceridemia. Three (7.8%) patients required dose reduction. Conclusion This real-world data confirms the efficacy of Lorlatinib in the second line and beyond with adverse effects matching that of registration studies.