Exploring the impact of patient-specific clinical features on osimertinib effectiveness in a real-world cohort of patients with EGFR mutated non-small cell lung cancer

Ard van Veelen, G. D.Marijn Veerman, Marjon V. Verschueren, Judith L. Gulikers, Christi M.J. Steendam, Anita J.W.M. Brouns, Safiye Dursun, Marthe S. Paats, Vivianne C.G. Tjan-Heijnen, Cor van der Leest, Anne Marie C. Dingemans, Ron H.J. Mathijssen, Ewoudt M.W. van de Garde, Patrick Souverein, Johanna H.M. Driessen, Lizza E.L. Hendriks, Robin M.J.M. van Geel, Sander Croes*

*Corresponding author for this work

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Abstract

Osimertinib is prescribed to patients with metastatic non-small cell lung cancer (NSCLC) and a sensitizing EGFR mutation. Limited data exists on the impact of patient characteristics or osimertinib exposure on effectiveness outcomes. This was a Dutch, multicenter cohort study. Eligible patients were ≥18 years, with metastatic EGFRm+ NSCLC, receiving osimertinib. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analyses and multivariate Cox proportional hazard models were performed. In total, 294 patients were included. Primary EGFR-mutations were mainly exon 19 deletions (54%) and p.L858R point mutations (30%). Osimertinib was given in first-line (40%), second-line (46%) or beyond (14%), with median PFS 14.4 (95% CI: 9.4-19.3), 13.9 (95% CI: 11.3-16.1) and 8.7 months (95% CI: 4.6-12.7), respectively. Patients with low BMI (<20.0 kg/m2) had significantly shorter PFS/OS compared to all other subgroups. Patients with a high plasma trough concentration in steady state (Cmin,SS; >271 ng/mL) had shorter PFS compared to a low Cmin,SS (<163 ng/mL; aHR 2.29; 95% CI: 1.13-4.63). A significant longer PFS was seen in females (aHR = 0.61, 95% CI: 0.45-0.82) and patients with the exon 19 deletion (aHR = 0.58, 95% CI: 0.36-0.92). A trend towards longer PFS was seen for TP53 wild-type patients, while age did not impact PFS. Patients with a primary EGFR exon 19 deletion had longer PFS, while a low BMI, male sex and a high Cmin,SS were indicative for shorter PFS and/or OS. Age was not associated with effectiveness outcomes of osimertinib.

Original languageEnglish
Pages (from-to)332-342
Number of pages11
JournalInternational Journal of Cancer
Volume154
Issue number2
Early online date15 Oct 2023
DOIs
Publication statusPublished - 15 Jan 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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