LOREALAUS: LOrlatinib REAL-World AUStralian Experience in Advanced ALK-Rearranged NSCLC

Marliese Alexander, B.Pharm(Hons), MPH, PhD; Joe Wei, MD; Sagun Parakh, MD; Thomas John, MD; Steven Kao, MD; Adnan Nagrial, MD; Samantha Bowyer, MD; Lydia Warburton, MD; Melissa Moore, MD; Brett G.M. Hughes, MD; Timothy D. Clay, MD; Nick Pavlakis, MD; Benjamin J. Solomon, MD; Malinda Itchins, MD

JTO Clinical and Research Reports (Apr 2023)

LOREALAUS: LOrlatinib REAL-World AUStralian Experience in Advanced ALK-Rearranged NSCLC

Marliese Alexander, B.Pharm(Hons), MPH, PhD,
Joe Wei, MD,
Sagun Parakh, MD,
Thomas John, MD,
Steven Kao, MD,
Adnan Nagrial, MD,
Samantha Bowyer, MD,
Lydia Warburton, MD,
Melissa Moore, MD,
Brett G.M. Hughes, MD,
Timothy D. Clay, MD,
Nick Pavlakis, MD,
Benjamin J. Solomon, MD,
Malinda Itchins, MD

Affiliations

Marliese Alexander, B.Pharm(Hons), MPH, PhD: Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia; Corresponding author. Address for correspondence: Marliese Alexander, B.Pharm(Hons), MPH, PhD, Peter MacCallum Cancer Centre, 305 Grattan Street Melbourne, Victoria 3000, Australia.
Joe Wei, MD: Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, New South Wales, Australia; Northern Clinical School, The University of Sydney, St. Leonards, New South Wales, Australia
Sagun Parakh, MD: Olivia Newton-John Cancer Research Institute, Austin Hospital, Heidelberg, Victoria, Australia; School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia
Thomas John, MD: Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
Steven Kao, MD: Chris O’Brien Lifehouse, Sydney, New South Wales, Australia; Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
Adnan Nagrial, MD: Department of Medical Oncology, Westmead Hospital, Westmead, New South Wales, Australia; Blacktown Hospital, Blacktown, New South Wales, Australia; Westmead Clinical School, The University of Sydney, Westmead, New South Wales, Australia
Samantha Bowyer, MD: Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; University of Western Australia, Perth, Western Australia, Australia
Lydia Warburton, MD: Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
Melissa Moore, MD: Department of Medical Oncology, St. Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia; Department of Medicine, The University of Melbourne, Carlton, Victoria, Australia
Brett G.M. Hughes, MD: Department of Medical Oncology, The Prince Charles Hospital, Brisbane, Queensland, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
Timothy D. Clay, MD: Department of Medical Oncology, Saint John of God Subiaco Hospital, Perth, Western Australia, Australia; Icon Cancer Care Midland, Western Australia, Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
Nick Pavlakis, MD: Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, New South Wales, Australia; Northern Clinical School, The University of Sydney, St. Leonards, New South Wales, Australia
Benjamin J. Solomon, MD: Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
Malinda Itchins, MD: Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, New South Wales, Australia; Northern Clinical School, The University of Sydney, St. Leonards, New South Wales, Australia

Journal volume & issue: Vol. 4, no. 4
p. 100490

Abstract

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Introduction: Over the past decade, ALK tyrosine kinase inhibitors have delivered unprecedented survival for individuals with ALK-positive (ALK+) lung cancers. Real-world data enhance the understanding of optimal drug sequencing and expectations for survival. Methods: Multicenter real-world study of individuals with pretreated advanced ALK+ lung cancers managed on a lorlatinib access program between 2016 and 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 and OSa), with at least 30 days (one-cycle) lorlatinib exposure (PFSb and OSb), and with good performance status (PFSc and OSc). Subgroups of interest were analyzed to assess signals of potential clinical applicability. Two OS index dates were analyzed, from lorlatinib initiation and advanced ALK+ diagnosis. Results: The population (N = 38, 10 sites) was heavily pretreated (23 had ≥2 previous treatment lines) with a high disease burden (26 had 2–4 sites and 11 had >4 sites of metastatic disease, 19 had brain metastases). The overall response rate was 44% and the disease control rate was 81%. Lorlatinib dose reduction (18%), interruption (16%), and discontinuation (3%) were consistent with the trial experience. From advanced ALK+ diagnosis, the median OS for populations a, b, and c was 45.0 months, 69.9 months and 61.2 months respectively. From lorlatinib initiation, the median PFSa, PFSb and PFSc was 7.3 months, 13.2 months and 27.7 months and the median OSa, OSb and OSc was 19.9 months, 25.1 months and 27.7 months. The median PFSa with versus without brain metastases was 34.6 months versus 5.8 months (p = 0.09). The intracranial median PFS was 14.2 months. Previous good response versus poor response to the first ALK-directed therapy median PFSa was 27.7 months versus 4.7 months with a hazard ratio of 0.3 (p = 0.01). Conclusions: Lorlatinib is a potent, highly active brain-penetrant third-generation ALK tyrosine kinase inhibitors with benefits for most individuals in the later-line setting in a real-world evaluation, consistent with clinical trial data.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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