Research Article|Articles in Press, 100490

LOREALAUS: LOrlatinib REAL world AUStralian experience in advanced anaplastic lymphoma kinase rearranged non-small cell lung cancer

Open AccessPublished:February 24, 2023DOI:
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      Over the past decade ALK-inhibitors (ALKi) have delivered unprecedented survival for individuals with ALK+ lung cancers. Real-world data enhance the understanding of optimal drug sequencing and expectations for survival.


      Multi-centre real-world study of individuals with pre-treated advanced ALK+ lung cancers managed on a lorlatinib access program between 2016-2020. Key outcomes were lorlatinib efficacy, tolerability, and treatment sequencing. Progression free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method among all individuals (PFSa/OSa), with ≥30 days (1-cycle) lorlatinib exposure (PFSb/OSb), and with good performance status (PFSc/OSc). Sub-groups of interest were analysed to assess signals of potential clinical applicability. Two OS index dates were analysed, from lorlatinib initiation and advanced ALK+ diagnosis.


      The population (n=38, 10 sites) were heavily pre-treated (23 had ≥2 prior treatment lines) with high disease burden (26 had 2-4 sites and 11 had >4 sites of metastatic disease, 19 had brain metastases). ORR was 44% and DCR was 81%. Lorlatinib dose reduction (18%), interruption (16%) and discontinuation (3%) were consistent with the trial experience. From advanced ALK+ diagnosis median (m) OSa/b/c was 45.0mo/69.9mo/61.2mo. From lorlatinib initiation mPFSa/b/c was 7.3mo/13.2mo/27.7mo and mOSa/b/c 19.9mo/25.1mo/27.7mo. With versus without brain metastases mPFSa was 34.6mo vs 5.8mo (P=0.09). Intracranial mPFS was 14.2mo. Previous good response versus poor response to first ALK directed therapy mPFSa was 27.7mo vs 4.7mo, HR 0.3, P=0.01.


      Lorlatinib is a potent, highly active brain penetrant third-generation ALKi with benefit for most individuals in the later line setting in a real-world evaluation, consistent with clinical trial data.