Early Weight Gain as a Risk Factor for Increased Maximum Weight Gain Among Patients With NSCLC on Lorlatinib and Other ALK Tyrosine Kinase Inhibitors

Abstract

Introduction

Therapy-associated weight gain affects the quality of life and health of patients with ALK-positive NSCLC treated with tyrosine kinase inhibitors (TKIs). The severity and timing of real-world weight gain on ALK TKIs and associated risk factors are poorly understood, impairing timely interventions.

Methods

A retrospective chart review of patients with ALK-positive NSCLC receiving TKIs at our institution from January 1, 2020 to December 31, 2023 was conducted. Demographics, metabolic comorbidities, treatment details, and clinic-measured weights were collected. The grade of weight gain, maximum weight gain (% of baseline), and early weight gain (within 6 mo of TKI start) were calculated. Univariable and multivariable linear mixed effects analyses for predictors of weight gain were performed.

Results

A total of 91 patients received 156 treatment lines of TKI. Patients receiving lorlatinib experienced significantly higher maximum weight gain (mean 13.5% [95% confidence interval 10.8–16.2]) than those receiving other TKIs (p <0.001). Any-grade and grade 3 weight gain rates exceeded those from clinical trials. In multivariate modeling, early weight gain of at least 5% within 6 months (p <0.001), lorlatinib use (p = 0.007), and age 50 years or younger (p = 0.046) were associated with maximum weight gain. Among patients receiving lorlatinib, early weight gain (p = 0.001) remained significantly associated with higher maximum weight gain.

Conclusions

In this real-world cohort, rates and severity of weight gain on ALK TKIs were higher than in registrational trials, and highest on lorlatinib. Patients with early weight gain of greater than or equal to 5% within 6 months developed higher maximum gain. Prospective investigation of early weight management interventions is encouraged.