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Lorlatinib Tolerability and Association With Clinical Outcomes in Patients With Advanced ALK- or ROS1-Rearranged

Rohit Thummalapalli1, Noura J Choudhury1, Fiona Ehrich2

  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

JTO Clinical and Research Reports
|August 30, 2023
PubMed
Abstract

Insights

Dose reductions for lorlatinib in advanced ALK- or ROS1-rearranged NSCLC did not negatively impact progression-free survival or overall survival. Managing adverse events through dose adjustments can maintain treatment efficacy.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Lorlatinib is used for advanced ALK- and ROS1-rearranged NSCLC, but adverse events (AEs) often necessitate dose reductions.
  • The impact of these dose reductions on patient outcomes is not well-established, particularly in later treatment lines.

Purpose of the Study:

  • To assess the frequency of lorlatinib dose reductions due to treatment-related AEs (TRAEs) in patients with advanced ALK- or ROS1-rearranged NSCLC.
  • To determine the association between these dose reductions and progression-free survival (PFS) and overall survival (OS).

Main Methods:

  • A retrospective multicenter analysis of 144 patients with advanced ALK- or ROS1-rearranged NSCLC treated with lorlatinib in the second-line or later settings.
  • Analysis included assessing TRAE-related dose reductions and their correlation with PFS and OS using Cox regression models.

Main Results:

  • 40% of patients (58/144) experienced dose reductions, primarily due to neurocognitive AEs or neuropathy (59%).
  • Median PFS was 8.1 months and median OS was 20.7 months for all patients.
  • Cox regression analysis showed no significant association between dose reduction and PFS (HR=0.86) or OS (HR=0.78).

Conclusions:

  • Dose reductions of lorlatinib in this patient population were not linked to worse clinical outcomes.
  • Early identification and management of TRAEs, including dose adjustments, may improve tolerability without sacrificing efficacy.
Keywords:
ALKLorlatinibNon–small cell lung cancerROS1Toxicity

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