95 Lorlatinib in advanced ALK-rearranged NSCLC - real-world experience in a UK population

Abstract

Background Lorlatinib, a third-generation tyrosine kinase inhibitor (TKI) for the treatment of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC), provides a treatment option following progression on first-line TKI. The recent CROWN study demonstrated good efficacy in first-line setting, although not currently reimbursed in the UK. We aimed to assess its efficacy and toxicity profile in a real-world observational UK urban population. Methods This multi-centre retrospective observational real-world study included pre-treated ALK-positive metastatic NSCLC patients, from 13 NHS trusts across London and SE England, who started lorlatinib from September 2016-January 2024. Clinical and demographic data were collected from electronic medical records. Key outcomes included best response, progression free (PFS) and overall survival (mOS) calculated using Kaplan-Meier method. Results Eighty-one patients (median age 52, range 20-83 years; 62% female; 57% never-smoker) were included. Ethnicity: White (52%), Asian (20%), and Black (12%). ALK testing was by IHC (37%), FISH (26%), or combination (23%). Seventy-nine percent were PS 0-1 at initiation of lorlatinib. Brain metastases were present in 27% at diagnosis, 26% following diagnosis but prior to lorlatinib. Three percent developed first brain metastases during/after lorlatinib therapy. Lorlatinib was most commonly administered second-line (63%). Objective response rate was 44%, with a further 22% achieving best response of stable disease. Median PFS for all patients was 9.5 months (m) and 5.5 m for second line; mOS was 17.2 m for all patients, 12.2 m for second line (figure). Toxicities were predominantly low-grade, including hyper-cholesterolaemia (54%), fatigue (36%), peripheral oedema (23%). Nine percent experienced grade >=3 psychosis or hallucinations. Only 4% of patients discontinued due to treatment-related toxicities. [Formula presented] Conclusion This real-world study confirms reported clinical data for both efficacy and tolerability of lorlatinib in a multi-ethnic UK population. Whilst toxicities are common, they were predominantly of low grade and resulted in few discontinuations. Disclosure No significant relationships.