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.

Autor: van Veelen A; Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.; CARIM School for Cardiovascular Disease, Maastricht University Medical Center+, Maastricht, The Netherlands.; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands., Veerman GDM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Verschueren MV; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.; Department of Clinical Pharmacy, St. Antonius Hospital, Utrecht/Nieuwegein, The Netherlands., Gulikers JL; Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.; CARIM School for Cardiovascular Disease, Maastricht University Medical Center+, Maastricht, The Netherlands., Steendam CMJ; Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Pulmonary Diseases, Catharina Hospital, Eindhoven, The Netherlands., Brouns AJWM; Department of Respiratory Medicine, Zuyderland, Geleen, The Netherlands.; Department of Pulmonary Diseases, GROW-School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands., Dursun S; Department of Pulmonary Diseases, GROW-School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands., Paats MS; Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., Tjan-Heijnen VCG; Department of Medical Oncology, Maastricht University Medical Center+, Maastricht, The Netherlands., van der Leest C; Department of Pulmonology, Amphia Hospital, Breda, The Netherlands., Dingemans AC; Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van de Garde EMW; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.; Department of Clinical Pharmacy, St. Antonius Hospital, Utrecht/Nieuwegein, The Netherlands., Souverein P; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands., Driessen JHM; Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.; CARIM School for Cardiovascular Disease, Maastricht University Medical Center+, Maastricht, The Netherlands.; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.; NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands., Hendriks LEL; Department of Pulmonary Diseases, GROW-School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands., van Geel RMJM; Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.; CARIM School for Cardiovascular Disease, Maastricht University Medical Center+, Maastricht, The Netherlands., Croes S; Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.; CARIM School for Cardiovascular Disease, Maastricht University Medical Center+, Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2024 Jan 15; Vol. 154 (2), pp. 332-342. Date of Electronic Publication: 2023 Oct 15.
DOI: 10.1002/ijc.34742
Abstrakt: 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/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.
(© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
Externí odkaz: