Exploring the impact of patient‐specific clinical features on osimertinib effectiveness in a real‐world cohort of patients with <i>EGFR</i> mutated non‐small cell lung cancer
Ard van Veelen, G. Veerman, Marjon V. Verschueren, Judith L. Gulikers, C. Steendam, A. Brouns, Safiye Dursun, Marthe S. Paats, Vivianne C. G. Tjan‐Heijnen, Cor van der Leest, Anne‐Marie C. Dingemans, Ron H.J. Mathijssen, E.M.W. van de Garde, Patrick C. Souverein, Johanna H. M. Driessen, Lizza Hendriks, Robin M.J.M. van Geel, Sander Croes
Abstract
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 EGFR m + 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/m 2 ) had significantly shorter PFS/OS compared to all other subgroups. Patients with a high plasma trough concentration in steady state (C min,SS ; >271 ng/mL) had shorter PFS compared to a low C min,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 C min,SS were indicative for shorter PFS and/or OS. Age was not associated with effectiveness outcomes of osimertinib.