RT Journal Article
T1 Association of ERBB Mutations With Clinical Outcomes of Afatinib- or Erlotinib-Treated Patients With Lung Squamous Cell Carcinoma: Secondary Analysis of the LUX-Lung 8 Randomized Clinical Trial.
A1 Goss, Glenwood D
A1 Felip, Enriqueta
A1 Cobo, Manuel
A1 Lu, Shun
A1 Syrigos, Konstantinos
A1 Lee, Ki Hyeong
A1 Göker, Erdem
A1 Georgoulias, Vassilis
A1 Li, Wei
A1 Guclu, Salih
A1 Isla, Dolores
A1 Min, Young Joo
A1 Morabito, Alessandro
A1 Ardizzoni, Andrea
A1 Gadgeel, Shirish M
A1 Fulop, Andrea
A1 Bühnemann, Claudia
A1 Gibson, Neil
A1 Kramer, Nicole
A1 Solca, Flavio
A1 Cseh, Agnieszka
A1 Ehrnrooth, Eva
A1 Soria, Jean-Charles
K1 Afatinib
K1 Carcinoma, Squamous Cell
K1 Disease-Free Survival
K1 Erlotinib Hydrochloride
K1 Genes, erbB
AB Treatment choice for lung squamous cell carcinoma could be aided by identifying predictive biomarkers. To assess whether patient outcomes in the LUX-Lung 8 trial were associated with ERBB gene family member aberrations in tumor specimens. Ad hoc secondary analysis of the LUX-Lung 8 trial conducted at 183 centers in 23 countries from March 30, 2012, to January 30, 2014. Eligible patients had stage IIIB or IV lung squamous cell carcinoma with progressive disease after 4 or more cycles of platinum-based chemotherapy. Tumor genetic analysis (TGA) was performed using next-generation sequencing in a cohort enriched for patients with progression-free survival (PFS) of more than 2 months. Epidermal growth factor receptor (EGFR) expression levels were assessed by immunohistochemistry in a separate cohort of patients from the LUX-Lung 8 population. Associations of PFS and overall survival (OS) with ERBB gene alterations and EGFR expression levels were assessed. This analysis was conducted from February 26, 2015, to June 12, 2017. Patients were randomized 1:1 to treatment with afatinib dimaleate (40 mg/d; n = 398) or erlotinib hydrochloride (150 mg/d; n = 397). Overall survival, PFS, pooled and individual ERBB gene mutations, ERBB copy number alterations, and EGFR expression. Tumor specimens from 245 patients were eligible for next-generation sequencing (TGA subset: 132 patients treated with afatinib; 113 patients treated with erlotinib). In this population, outcomes were improved with afatinib vs erlotinib treatment (PFS: median, 3.5 vs 2.5 months; hazard ratio [HR], 0.69; 95% CI, 0.51-0.92; P = .01; OS: median, 8.4 vs 6.6 months; HR, 0.81; 95% CI, 0.62-1.05; P = .12). Of 245 patients in the TGA subset, 53 (21.6%) had tumors with 1 or more ERBB mutations. Among afatinib-treated patients, PFS (median, 4.9 vs 3.0 months; HR, 0.62; 95% CI, 0.37-1.02; P = .06) and OS (median, 10.6 vs 8.1 months; HR, 0.75; 95% CI, 0.47-1.17; P = .21) were longer among those with ERBB mutation-positive disease than among those without. The presence of HER2 mutations was associated with favorable PFS and OS following afatinib vs erlotinib treatment. There was no apparent association between copy number alteration or EGFR expression level and outcome. Next-generation sequencing may help identify patients with lung squamous cell carcinoma who would derive additional benefit from treatment with afatinib. The role of ERBB mutations, particularly HER2 mutations, as predictive biomarkers for afatinib treatment in this setting warrants further evaluation. ClinicalTrials.gov Identifier: NCT01523587.
PB American Medical Association
YR 2018
FD 2018-01-25
LK http://hdl.handle.net/10668/12594
UL http://hdl.handle.net/10668/12594
LA en
NO Goss GD, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, et al. Association of ERBB Mutations With Clinical Outcomes of Afatinib- or Erlotinib-Treated Patients With Lung Squamous Cell Carcinoma: Secondary Analysis of the LUX-Lung 8 Randomized Clinical Trial. JAMA Oncol. 2018 Sep 1;4(9):1189-1197
DS RISalud
RD Apr 18, 2025