Favorable survival outcomes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer sequentially treated with a tyrosine kinase inhibitor and osimertinib in a real-world setting.
EGFR T790M mutation
EGFR-mutated NSCLC
Osimertinib
Rebiopsy
Second line
Sequential therapy
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
13
12
2022
accepted:
03
05
2023
medline:
31
7
2023
pubmed:
18
5
2023
entrez:
17
5
2023
Statut:
ppublish
Résumé
EGFR tyrosine kinase inhibitor (TKI) therapy in EGFR-mutated lung cancer is limited by acquired resistance. In half of the patients treated with first/second-generation (1st/2nd gen) TKI, resistance is associated with EGFR p.T790M mutation. Sequential treatment with osimertinib is highly active in such patients. Currently, there is no approved targeted second-line option for patients receiving first-line osimertinib, which thus may not be the best choice for all patients. The present study aimed to evaluate the feasibility and efficacy of a sequential TKI treatment with 1st/2nd gen TKI, followed by osimertinib in a real-world setting. Patients with EGFR-mutated lung cancer treated at two major comprehensive cancer centers were retrospectively analyzed by the Kaplan-Meier method and log rank test. A cohort of 150 patients, of which 133 received first-line treatment with a first/second gen EGFR TKI, and 17 received first-line osimertinib, was included. Median age was 63.9 years, 55% had ECOG performance score of ≥ 1. First-line osimertinib was associated with prolonged progression-free survival (P = 0.038). Since the approval of osimertinib (February 2016), 91 patients were under treatment with a 1st/2nd gen TKI. Median overall survival (OS) of this cohort was 39.3 months. At data cutoff, 87% had progressed. Of those, 92% underwent new biomarker analyses, revealing EGFR p.T790M in 51%. Overall, 91% of progressing patients received second-line therapy, which was osimertinib in 46%. Median OS with sequenced osimertinib was 50 months. Median OS of patients with p.T790M-negative progression was 23.4 months. Real-world survival outcomes of patients with EGFR-mutated lung cancer may be superior with a sequenced TKI strategy. Predictors of p.T790M-associated resistance are needed to personalize first-line treatment decisions.
Identifiants
pubmed: 37198447
doi: 10.1007/s00432-023-04839-3
pii: 10.1007/s00432-023-04839-3
pmc: PMC10374675
doi:
Substances chimiques
osimertinib
3C06JJ0Z2O
Tyrosine Kinase Inhibitors
0
ErbB Receptors
EC 2.7.10.1
Protein Kinase Inhibitors
0
Aniline Compounds
0
EGFR protein, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9243-9252Informations de copyright
© 2023. The Author(s).
Références
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Cancer Discov. 2014 Sep;4(9):1046-61
pubmed: 24893891
Ther Adv Med Oncol. 2021 Mar 24;13:1758835921996509
pubmed: 34408792
N Engl J Med. 2018 Jan 11;378(2):113-125
pubmed: 29151359
Ann Oncol. 2020 Nov;31(11):1536-1544
pubmed: 32861806
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
pubmed: 10655437
Lancet Oncol. 2017 Nov;18(11):1454-1466
pubmed: 28958502
Nature. 2014 Jul 31;511(7511):543-50
pubmed: 25079552
Clin Cancer Res. 2013 Apr 15;19(8):2240-7
pubmed: 23470965
N Engl J Med. 2010 Jun 24;362(25):2380-8
pubmed: 20573926
J Clin Oncol. 2013 Sep 20;31(27):3327-34
pubmed: 23816960
N Engl J Med. 2020 Jan 2;382(1):41-50
pubmed: 31751012
N Engl J Med. 2009 Sep 3;361(10):958-67
pubmed: 19692684
J Thorac Oncol. 2018 Aug;13(8):1138-1145
pubmed: 29874546
Nature. 2021 Sep;597(7878):732-737
pubmed: 34526717
J Clin Oncol. 2020 Jan 10;38(2):124-136
pubmed: 31411950
Lancet Oncol. 2019 Dec;20(12):1655-1669
pubmed: 31591063
Lancet Oncol. 2014 Feb;15(2):213-22
pubmed: 24439929
Lancet Oncol. 2019 May;20(5):625-635
pubmed: 30975627
Ann Oncol. 2019 Aug 1;30(8):1311-1320
pubmed: 31086949
Oncogene. 2008 Aug 7;27(34):4702-11
pubmed: 18408761
N Engl J Med. 2017 Feb 16;376(7):629-640
pubmed: 27959700
Lung Cancer. 2020 Jan;139:133-139
pubmed: 31786475
Oncotarget. 2016 Nov 29;7(48):78985-78993
pubmed: 27738317
J Thorac Oncol. 2017 Feb;12(2):403-407
pubmed: 27765535
Front Oncol. 2020 Sep 04;10:1481
pubmed: 33014788
Lancet Oncol. 2012 Mar;13(3):239-46
pubmed: 22285168