Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases
Journal
Journal of Thoracic Oncology
Journal Volume
15
Journal Issue
5
Pages
803-815
Date Issued
2020
Author(s)
Abstract
Introduction: Limited clinical data are available regarding the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) in patients with NSCLC harboring uncommon EGFR mutations. This pooled analysis assessed the activity of afatinib in 693 patients with tumors harboring uncommon EGFR mutations treated in randomized clinical trials, compassionate-use and expanded-access programs, phase IIIb trials, noninterventional trials, and case series or studies. Methods: Patients had uncommon EGFR mutations, which were categorized as follows: (1) T790M; (2) exon 20 insertions; (3) “major” uncommon mutations (G719X, L861Q, and S768I, with or without any other mutation except T790M or an exon 20 insertion); (4) compound mutations; and (5) other uncommon mutations. Key end points were overall response rate (ORR), duration of response, and time to treatment failure (TTF). Results: In EGFR TKI–naive patients (n = 315), afatinib demonstrated activity against major uncommon mutations (median TTF = 10.8 mo; 95% confidence interval [CI]: 8.1–16.6; ORR = 60.0%), compound mutations (median TTF = 14.7 mo; 95% CI: 6.8–18.5; ORR = 77.1%), other uncommon mutations (median TTF = 4.5 mo; 95% CI: 2.9–9.7; ORR = 65.2%), and some exon 20 insertions (median TTF = 4.2 mo; 95% CI: 2.8–5.3; ORR = 24.3%). The median duration of response for major uncommon mutations, compound mutations, other uncommon mutations, and some exon 20 insertions was 17.1, 16.6, 9.0, and 11.9 months, respectively. Activity of afatinib was also observed in EGFR TKI–pretreated patients (n = 378). A searchable database of these outcomes by individual genotype was generated. Conclusions: Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutations. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings. ? 2020 International Association for the Study of Lung Cancer
Subjects
Afatinib; Compound EGFR mutation; NSCLC; Uncommon EGFR mutations
SDGs
Other Subjects
afatinib; vasculotropin receptor; afatinib; EGFR protein, human; epidermal growth factor receptor; protein kinase inhibitor; adult; aged; antineoplastic activity; Article; case study; controlled study; drug efficacy; EGFR gene; exon; female; gene; gene insertion; gene mutation; genotype; human; major clinical study; male; non small cell lung cancer; phase 3 clinical trial; priority journal; randomized controlled trial; treatment response; clinical trial; genetics; lung tumor; mutation; Afatinib; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
Publisher
Elsevier Inc
Type
journal article