Chor-Kuan Lim1, Yu-Feng Wei2, Mao-Song Tsai3, Kuan-Yu Chen4, Jin-Yuan Shih5, Chong-Jen Yu5. 1. Division of Pulmonary Medicine, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei, Taiwan; Oriental Institute of Technology, New Taipei, Taiwan. 2. Division of Pulmonary Medicine, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan. 3. Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei, Taiwan. 4. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: tuff.chen@msa.hinet.net. 5. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
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.
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.
Authors: Anna Mueller-Schoell; Stefanie L Groenland; Oliver Scherf-Clavel; Madelé van Dyk; Wilhelm Huisinga; Robin Michelet; Ulrich Jaehde; Neeltje Steeghs; Alwin D R Huitema; Charlotte Kloft Journal: Eur J Clin Pharmacol Date: 2020-11-09 Impact factor: 2.953