Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
received:
15
11
2022
revised:
03
02
2023
accepted:
08
03
2023
medline:
2
6
2023
pubmed:
14
3
2023
entrez:
13
3
2023
Statut:
ppublish
Résumé
The uncommon EGFR exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared with the common ex19del, E746_A750del in preclinical models. The clinical efficacy of osimertinib in patients with non-small cell lung cancer harboring L747_A750>P and other uncommon ex19dels is not known. The AACR GENIE database was interrogated to characterize the frequency of individual ex19dels relative to other variants, and a multicenter retrospective cohort was used to compare clinical outcomes for patients with tumors harboring E746_A750del, L747_A750>P, and other uncommon ex19dels who received osimertinib in the first line (1L) or in second or later lines of therapy and were T790M+ (≥2L). ex19dels comprised 45% of EGFR mutations, with 72 distinct variants ranging in frequency from 28.1% (E746_A750del) to 0.03%, with L747_A750>P representing 1.8% of the EGFR mutant cohort. In our multi-institutional cohort (N = 200), E746_A750del was associated with significantly prolonged progression-free survival (PFS) with 1L osimertinib versus L747_A750>P [median 21.3 months (95% confidence interval, 17.0-31.7) vs. 11.7 months (10.8-29.4); adjusted HR 0.52 (0.28-0.98); P = 0.043]. Osimertinib efficacy in patients with other uncommon ex19dels varied on the basis of the specific mutation present. The ex19del L747_A750>P is associated with inferior PFS compared with the common E746_A750del mutation in patients treated with 1L osimertinib. Understanding differences in osimertinib efficacy among EGFR ex19del subtypes could alter management of these patients in the future.
Identifiants
pubmed: 36913537
pii: 718746
doi: 10.1158/1078-0432.CCR-22-3497
pmc: PMC10493186
mid: NIHMS1883691
doi:
Substances chimiques
osimertinib
3C06JJ0Z2O
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
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2123-2130Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA196530
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA233414
Pays : United States
Informations de copyright
©2023 American Association for Cancer Research.
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