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
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/1/1
Y1 - 2019/1/1
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.
AB - 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.
KW - EGFR-activating mutations
KW - Early access program
KW - Non-small cell lung cancer
KW - Osimertinib
KW - T790M EGFR mutation
KW - Tyrosine-kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85057474321&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2018.11.037
DO - 10.1016/j.lungcan.2018.11.037
M3 - Article
C2 - 30642559
AN - SCOPUS:85057474321
SN - 0169-5002
VL - 127
SP - 96
EP - 102
JO - Lung Cancer
JF - Lung Cancer
ER -