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Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation.
Lung Cancer. 2019 01; 127:96-102.LC

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.

Authors+Show Affiliations

Hôpital Quesnay, Mantes-la-Jolie, France. Electronic address: j-b.auliac@ch-mantes-la-jolie.fr.Centre Léon Bérard, Lyon, France.Hôpital Gustave Roussy, Villejuif, France.CHI de Créteil, France.Hôpital Tenon, Paris, France.Hôpital Foch, Suresnes, France.CHU Charles Nicolle, Rouen, France.CHU de Tours, France.Aix Marseille Univ, APHM, CNRS, INSERM, CRCM, Department of Multidisciplinary Oncology & Therapeutic Innovations, Marseille, France.CHU de Lyon, France.CH Annecy Genevois, Annecy, France.Centre Paul Strass, Strasbourg, France.Institut Bergonie, Bordeaux, France.Hôpital Cochin, Paris, France.CHRU de Lille, France.CHU de Lyon, France.Centre Hospitalier de Pau, France.Institut Curie, Paris, France.Centre Hospitalier de Villefranche-sur-Saône, France.CHI de Créteil, France.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30642559

Citation

Auliac, Jean Bernard, et al. "Real-life Efficacy of Osimertinib in Pretreated Patients With Advanced Non-small Cell Lung Cancer Harboring EGFR T790M Mutation." Lung Cancer (Amsterdam, Netherlands), vol. 127, 2019, pp. 96-102.
Auliac JB, Pérol M, Planchard D, et al. Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation. Lung Cancer. 2019;127:96-102.
Auliac, J. B., Pérol, M., Planchard, D., Monnet, I., Wislez, M., Doubre, H., Guisier, F., Pichon, E., Greillier, L., Mastroianni, B., Decroisette, C., Schott, R., Le Moulec, S., Arrondeau, J., Cortot, A. B., Gerinière, L., Renault, A., Daniel, C., Falchero, L., & Chouaid, C. (2019). Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation. Lung Cancer (Amsterdam, Netherlands), 127, 96-102. https://doi.org/10.1016/j.lungcan.2018.11.037
Auliac JB, et al. Real-life Efficacy of Osimertinib in Pretreated Patients With Advanced Non-small Cell Lung Cancer Harboring EGFR T790M Mutation. Lung Cancer. 2019;127:96-102. PubMed PMID: 30642559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation. AU - Auliac,Jean Bernard, AU - Pérol,Maurice, AU - Planchard,David, AU - Monnet,Isabelle, AU - Wislez,Marie, AU - Doubre,Hélène, AU - Guisier,Florian, AU - Pichon,Eric, AU - Greillier,Laurent, AU - Mastroianni,Bénédicte, AU - Decroisette,Chantal, AU - Schott,Roland, AU - Le Moulec,Sylvestre, AU - Arrondeau,Jennifer, AU - Cortot,Alexis B, AU - Gerinière,Laurence, AU - Renault,Aldo, AU - Daniel,Catherine, AU - Falchero,Lionel, AU - Chouaid,Christos, Y1 - 2018/11/27/ PY - 2018/07/26/received PY - 2018/11/13/revised PY - 2018/11/27/accepted PY - 2019/1/16/entrez PY - 2019/1/16/pubmed PY - 2019/12/28/medline KW - EGFR-activating mutations KW - Early access program KW - Non-small cell lung cancer KW - Osimertinib KW - T790M EGFR mutation KW - Tyrosine-kinase inhibitors SP - 96 EP - 102 JF - Lung cancer (Amsterdam, Netherlands) JO - Lung Cancer VL - 127 N2 - 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. SN - 1872-8332 UR - https://www.unboundmedicine.com/medline/citation/30642559/Real_life_efficacy_of_osimertinib_in_pretreated_patients_with_advanced_non_small_cell_lung_cancer_harboring_EGFR_T790M_mutation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169-5002(18)30677-9 DB - PRIME DP - Unbound Medicine ER -