Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation. (January 2019)

• Record Type: Journal Article
• Authors: Auliac, Jean Bernard; Pérol, Maurice; Planchard, David; Monnet, Isabelle; Wislez, Marie; Doubre, Hélène; Guisier, Florian; Pichon, Eric; Greillier, Laurent; Mastroianni, Bénédicte; Decroisette, Chantal; Schott, Roland; Le Moulec, Sylvestre; Arrondeau, Jennifer; Cortot, Alexis B.; Gerinière, Laurence; Renault, Aldo; Daniel, Catherine; Falchero, Lionel; Chouaid, Christos
• Is Part Of: Lung cancer. Volume 127(2019)
• Page Start: 96
• Page End: 102
• Publication Date: 2019-01
• Subjects: Non-small cell lung cancer -- Tyrosine-kinase inhibitors -- T790M EGFR mutation -- EGFR-activating mutations -- Osimertinib -- Early access program; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.11.037
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Efficacy of osimertinib in real-world setting and in clinical trials was comparable. Osimertinib was efficient in patients with brain metastasis. Osimertinib was efficient in second or more lines in T790 M EGFR-mutated patients. EGFR exon 19 deletion had a better susceptibility to osimertinib. Abstract: Objectives The efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR T790 M resistance mutation was demonstrated in clinical trials. However, data on efficacy of osimertinib in real world remain rare. Materials and methods This retrospective multicentric study analyzed T790M-positive advanced NSCLC patients enrolled in French early access program for osimertinib. Patients were pretreated with first- or second-generation EGFR tyrosine-kinase inhibitor and for a majority with chemotherapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. Results 205 patients (mean age, 69.5 years; female, 68.8%; adenocarcinoma, 97.5%, never-smokers, 71.5%) were analyzed. Osimertinib was used in second and third line in 18.0% and 82.0% of patients, respectively. Median PFS was 12.4 (95% CI, 10.1–15.1) months. In patients with and without cerebral metastasis, PFS was 9.7 (7.7–13.5) and 15.1 (12.0–17.1) months (p = 0.21), respectively. PFS in second and third line or more was 12.6 (6.7–17.5) and 12.4 (9.7–15.3) months, respectively. Median PFS in patients with EGFR exon 19 deletion and exon 21 mutation was 13.5 (10.1–16.0) and 9.7 (7.4–13.2) months, respectively (p = 0.049). Median OS since osimertinib initiation was 20.5 (16.9–24.3) months: 23.1 (18.6–27.8) and 18.0 (12.2–22.2) months in patients without and with cerebral metastasis (p = 0.11); 17.5 (11.6–27.8) and 21.7 (17.3–24.3) months as second or third line of treatment or more (p = 0.46), respectively. Median OS in patients with EGFR exon 19 deletion and exon 21 mutation was 23.1 (18.6–25.7) and 15.3 (11.6–21.7) months, respectively (p = 0.03). Osimertinib dosage was modified in 8.0% of patients and definitively discontinued for adverse events in 5.9%. Fifty patients benefited from rebiopsy (persistence of T790 M mutation, 44.7%; C797S mutation, 21.1%; cMET amplification, 8.0%). Conclusion In pretreated patients with T790M-mutated advanced NSCLC, the efficacy of osimertinib appears similar in real-world setting to that of clinical trials.