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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:https://doi.org/10.1016/j.jtocrr.2023.100490
LOREALAUS: LOrlatinib REAL world AUStralian experience in advanced anaplastic lymphoma kinase rearranged non-small cell lung cancer
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      ABSTRACT

      Introduction

      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.

      Methods

      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.

      Results

      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.

      Conclusion

      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.

      Article info

      Publication history

      Accepted: February 21, 2023
      Received in revised form: February 14, 2023
      Received: December 27, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      CONFLICT OF INTEREST DECLARATIONS

      Marliese Alexander: Travel sponsorship: AZ. Advisory Boards: Pfizer/BMS

      Joe Wei: none

      Sagun Parakh: Advisory Boards: AZ, MSD. Speaking Honoraria: Roche, BMS. Research Funding: Bayer, Roche.

      Thomas John: Advisory Boards: Roche, Merck, MSD, Puma, AstraZeneca, BMS, Novartis, Amgen, Gilead, PharmaMar, Specialised Therapeutics.

      Steven Kao: Speaking honoraria: MSD, BMS, AstraZeneca, Pfizer, Roche and Boehringer. Travel sponsorship: Boehringer.

      Adnan Nagrial: Advisory Boards: BMS, MSD, AZ, Pfizer, Roche, Takeda

      Samantha Bowyer: Advisory Boards: MSD, Lilly, Ipsen, Sanofi. Speaking honoraria: MSD. Travel sponsorship: Astrazeneca.

      Lydia Warburton: Advisory boards: MSD, Novartis, BMS. Speaking honoraria: MSD. Travel/educational sponsorship: MSD, BMS, AstraZeneca, Novartis.

      Melissa Moore: Advisory boards: Beigene, Takeda. Speaking honoraria: Astra Zeneca

      Brett GM Hughes: Advisory boards: MSD, BMS, Roche, Pfizer, AZ, Eisai, Takeda, Sanofi; Research Funding: Amgen.

      Timothy D Clay: Ownership interests: ClinicIQ. Advisory Boards: AstraZeneca/MedImmune, Cipla, Foundation Medicine, Takeda, Merk KgaA, Merck/Pfizer, Ipsen. Speakers Bureau: AstraZeneca/MedImmune, MSD. Honoraria: Specialised Therapeutics, Wiley, Lilly, Roche. Research Funding: Exelixis, Immutep, Clovis oncology, MSD Oncology, Pfizer, Amgen, Daiichi Sankyo/AstraZeneca, Abbvie, Janssen Oncology, BeiGene, Bayer, BridgeBio Pharm, BMS GmbH & Co. KG. Travel: AstraZeneca.

      Nick Pavlakis: Advisory Boards: Boehringer Ingelheim, MSD, Merck, BMS, Astra Zeneca, Takeda, Pfizer, Roche, Amgen, Beigene, Novartis, AllVascular. Speaking Honoraria: Boehringer Ingelheim, Pfizer, Roche, Takeda, Pierre-Faber. Research Funding: Bayer, Pfizer, Roche.

      Benjamin J Solomon: Advisory Boards/Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Merck, Bristol Myers Squibb, Eli Lilly, Amgen, BeiGene, Janssen, Takeda

      Malinda Itchins: Advisory Boards: Pfizer, Takeda, Bayer, MSD, Amgen, Merck, Roche, BeiGene. Honoraria: Pfizer, AstraZeneca, Takeda, Roche, Novartis, BMS, MSD, Bayer. Consultancy: Roche, Merck. Research Grants: Pfizer

      AUTHOR CONTRIBUTIONS

      The study was conceived and designed by MI, MA, BS, and NP. All authors contributed to data collection. Material preparation and analysis were performed by MA and MI. The first draft of the manuscript was written by MA and MI, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

      Identification

      DOI: https://doi.org/10.1016/j.jtocrr.2023.100490

      Copyright

      © 2023 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.

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