Teresa Moran1, Alvaro Taus2, Edurne Arriola2, Carlos Aguado3, Manuel Dómine4, Ana Gómez Rueda5, Antonio Calles6, Susana Cedrés7, Nuria Viñolas8, Dolores Isla9, Ramón Palmero10, María Sereno11, Victor Diaz12, Oscar Juan13, Raquel Marsé14, Paloma Martín Martorell15, José Miguel Sánchez Torres16. 1. 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. 2. Medical Oncology Department, Hospital del Mar-CIBERONC, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 3. Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain. 4. Medical Oncology Department, Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain. 5. Medical Oncology Department, IRYCIS, Ramón y Cajal University Hospital, Madrid, Spain. 6. Early Drug Development and Phase I Unit, Medical Oncology Department, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 7. Medical Oncology Department, Vall d'Hebron Hospital and Institute of Oncology, Barcelona, Spain. 8. Medical Oncology Department, Hospital Clinic i Provincial, Barcelona, Spain. 9. Medical Oncology Department, University Hospital Lozano Blesa, Zaragoza, Spain. 10. Medical Oncology Department, ICO-Duran i Reynalds, L'Hospitalet de Llobregat, Spain. 11. Medical Oncology Department, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Spain. 12. Medical Oncology Department, Hospital Sureste, Madrid, Spain. 13. Medical Oncology Department, Hospital Universitario La Fe, Valencia, Spain. 14. Medical Oncology Department, Son Espases, Palma de Mallorca, Spain. 15. Medical Oncology Department, Hospital Clínico Universitario, Valencia, Spain. 16. Medical Oncology Department, Hospital de la Princesa, Madrid, Spain.
Abstract
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.
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.