Treatment effectiveness and tolerability of afatinib at different doses in patients with EGFR-mutated lung adenocarcinoma: How low can we go?. (November 2018)

• Record Type: Journal Article
• Authors: Lim, Chor-Kuan; Wei, Yu-Feng; Tsai, Mao-Song; Chen, Kuan-Yu; Shih, Jin-Yuan; Yu, Chong-Jen
• Is Part Of: European journal of cancer. Volume 103(2018)
• Page Start: 32
• Page End: 40
• Publication Date: 2018-11
• Subjects: Afatinib -- EGFR -- Lung adenocarcinoma -- Effectiveness -- Tyrosine kinase inhibitor; EGFR epidermal growth factor receptor -- NHI National Health Insurance -- TKI tyrosine kinase inhibitor -- ECOG Eastern Cooperative Oncology Group -- DNA deoxyribonucleic acid -- PCR polymerase chain reaction -- PD progressive disease -- PFS progression-free survival -- RR response rate -- DCR disease control rate; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.07.128
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Introduction: Afatinib is commonly used as the first-line treatment for EGFR -mutated lung adenocarcinoma. However, dose adjustments are frequently required. This study aimed to investigate the treatment effectiveness of afatinib administered at different doses to patients with EGFR -mutated lung adenocarcinoma. Methods: Treatment-naïve patients with advanced EGFR -mutated lung adenocarcinoma who received afatinib therapy between May 2014 and September 2016 were enrolled retrospectively. Collected clinical data included age, sex, smoking history, performance status, disease stages, EGFR mutation status, initial doses of afatinib, dose adjustments, treatment responses, progression-free survival and treatment-associated adverse events. The average daily dose was calculated by dividing the summation of all doses of prescribed tablets during the treatment period by the total days of afatinib use. The patients were classified into five treatment groups based on average daily doses: 40 mg, <40 and >30 mg, 30 mg, <30 and ≥ 20 mg and <20 mg. Results: A total of 254 patients were included. No significant differences were found among these five treatment groups with respect to response rates (69.3%, 68.3%, 70.5%, 77.8% and 66.7%, respectively, p = 0.920) and disease control rates (97.4%, 95.2%, 97.7%, 100% and 100%, respectively, p = 0.749). However, the treatment group with an average daily dose of <20 mg had a significant shorter progression-free survival as compared with the other groups (16.8, 12.4, 13.9, 17.0 and 5.3 months, respectively, p = 0.049). Conclusions: Dose reduction may not affect the treatment effectiveness until the average daily dose is below 20 mg. Further prospective studies of afatinib therapy at different daily doses are warranted. Highlights: Afatinib 40 mg once daily is recommended for treatment of EGFR –mutated NSCLC, but dose reduction is frequently required. The treatment effectiveness of afatinib is comparable at an average daily dose ranging from 40 mg to 20 mg. An average daily dose below 20 mg may affect the treatment effectiveness.