Clinical Activity of Afatinib in Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Spanish Retrospective Multicenter Study.

Autor: Moran T; Medical Oncology Department, Catalan Institute of Oncology and Applied Research Group in Oncology (B-ARGO), Badalona, Spain; Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain. Electronic address: mmoran@iconcologia.net., Taus A; Medical Oncology Department, Hospital del Mar-CIBERONC, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain., Arriola E; Medical Oncology Department, Hospital del Mar-CIBERONC, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain., Aguado C; Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain., Dómine M; Medical Oncology Department, Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain., Rueda AG; Medical Oncology Department, IRYCIS, Ramón y Cajal University Hospital, Madrid, Spain., Calles A; Early Drug Development and Phase I Unit, Medical Oncology Department, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain., Cedrés S; Medical Oncology Department, Vall d'Hebron Hospital and Institute of Oncology, Barcelona, Spain., Viñolas N; Medical Oncology Department, Hospital Clinic i Provincial, Barcelona, Spain., Isla D; Medical Oncology Department, University Hospital Lozano Blesa, Zaragoza, Spain., Palmero R; Medical Oncology Department, ICO-Duran i Reynalds, L'Hospitalet de Llobregat, Spain., Sereno M; Medical Oncology Department, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Spain., Diaz V; Medical Oncology Department, Hospital Sureste, Madrid, Spain., Juan O; Medical Oncology Department, Hospital Universitario La Fe, Valencia, Spain., Marsé R; Medical Oncology Department, Son Espases, Palma de Mallorca, Spain., Martorell PM; Medical Oncology Department, Hospital Clínico Universitario, Valencia, Spain., Sánchez Torres JM; Medical Oncology Department, Hospital de la Princesa, Madrid, Spain.
Jazyk: angličtina
Zdroj: Clinical lung cancer [Clin Lung Cancer] 2020 Sep; Vol. 21 (5), pp. 428-436.e2. Date of Electronic Publication: 2020 Apr 25.
DOI: 10.1016/j.cllc.2020.04.011
Abstrakt: Introduction: Uncommon epidermal growth factor receptor (EGFR) mutations (u-EGFRm) are a heterogeneous group of molecular alterations and have also been reported as comutations with other EGFR mutations (complex mutations) in non-small-cell lung cancer (NSCLC). Afatinib has shown activity against some u-EGFRm, and we examined its efficacy in Spanish clinical practice.
Patients and Methods: Data of 67 patients with advanced NSCLC with u-EGFRm treated with afatinib between 2012 and 2017 at 23 Spanish institutions were reviewed. u-EGFRm were analyzed as complex mutations (group A), EGFR exon 20 insertions (ins20; group B), or single mutations (group C). Efficacy was evaluated in terms of overall survival (OS) and tumor response.
Results: Group A complex u-EGFRm consisted of double mutations of G719X+E709F, G719X+S768I, G719X+L861Q, L858R+T790M, L858R+S768I, L858R+S765I, del19+S768I, del19+L747S, or R776C+L861Q. No differences in clinical characteristics were found between groups A (n = 20), B (n = 23), and C (n = 24). Afatinib was administered as first-line therapy in 80% of patients. Median time of receipt of therapy was 4.2 months (range, 2.0-12.9 months). Median OS for the entire cohort was 19.9 months (95% confidence interval, 9.7, 30.1). Hazard ratios for OS were 0.26 (95% confidence interval, 0.10, 0.71; P = .008) and 0.40 (95% confidence interval, 0.17, 0.95; P = .037) for groups A and C compared to B, respectively. Response was significantly higher in groups A (70%) and C (54%) compared to B (13%; pairwise comparison P < .001 and .008, respectively).
Conclusion: In clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit with afatinib.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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