PCN68 An Incremental Effectiveness Analysis of Lorlatinib for the Treatment of ALK-Positive Advanced Non-Small Cell Lung Cancer that has Progressed after Another ALK Tyrosine Kinase Inhibitor in Portugal

To evaluate the incremental effectiveness of anaplastic lymphoma kinase (ALK) inhibitor lorlatinib compared to platinum-based chemotherapy (PBC) for adult patients with ALK-positive advanced non-small cell lung cancer (NSCLC) whose disease progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy or after crizotinib and at least one other ALK TKI in the Portuguese setting. A partitioned-survival model was developed, with progression-free survival (PFS), overall survival (OS), and time on treatment (ToT) for lorlatinib obtained through parametric survival models fit to data from the single-arm phase I/II trial B7461001. For PBC, PFS was modelled using a hazard ratio (HR) estimated from a matching-adjusted indirect comparison based on the B7461001 trial for lorlatinib and a retrospective chart review study for PBC. No OS data were available for PBC in the relevant populations, hence the PFS HR was used as a proxy for the OS HR. PBC ToT was assumed to be equal to PFS. Utility weights for pre-progression and post-progression on lorlatinib were based on the B7461001 trial, and the utility weight for post-progression after PBC or lorlatinib was found in the literature. A lifetime horizon was used. Deterministic and probabilistic sensitivity analyses were conducted. Treatment with lorlatinib allowed for a gain of 1.87 life years (LYs) or 1.40 quality-adjusted life years (QALYs) in patients whose disease progressed after alectinib or ceritinib and a gain of 1.57 LYs or 1.04 QALYs in patients whose disease progressed after crizotinib and another ALK TKI. Sensitivity analyses showed that the model was robust to parameter variation, except for the extrapolations of OS and ToT for lorlatinib. Lorlatinib results in increased life expectancy and quality-adjusted life expectancy compared with PBC in previously treated adult patients with ALK-positive NSCLC in the Portuguese setting.