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.
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