Toshihide Yokoyama1, Hiroshige Yoshioka2, Daichi Fujimoto3, Yoshiki Demura4, Katsuya Hirano5, Takahiro Kawai6, Ryogo Kagami7, Yasuyoshi Washio1, Tadashi Ishida1, Mariko Kogo3, Keisuke Tomii3, Takehiro Okuno4, Masaya Akai4, Masataka Hirabayashi5, Takashi Nishimura6, Yasuharu Nakahara7, Young Hak Kim8, Chisato Miyakoshi9, Kenichi Yoshimura10, Toyohiro Hirai8. 1. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan. 2. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan; Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan. Electronic address: hgyoshioka@gmail.com. 3. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 4. Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan. 5. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan. 6. Department of Respiratory Medicine, Kyoto-Katsura Hospital, Kyoto, Japan. 7. Department of Respiratory Medicine, Himeji Medical Center, Himeji, Japan. 8. Department of Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan. 9. Clinical Research Center, Kobe City Medical Center General Hospital, Kobe, Japan. 10. Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan.
Abstract
OBJECTIVES: Afatinib is an effective treatment in patients who have epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), but its toxicities often require dose adjustment. Exploratory analyses of previous trials have suggested that reducing the dose of afatinib can decrease treatment-related adverse events without negatively affecting effectiveness. The aim of this study was to assess the efficacy and safety of low starting dose of afatinib with dose modification according to its toxicity in patients with EGFR mutation-positive NSCLC. MATERIALS AND METHODS: This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib starting in a dose of 20 mg/day. If tolerated, the dose was increased in 10-mg increments up to 50 mg/day. The primary endpoint was progression-free survival (PFS). RESULTS: From February 2015 through March 2016, 46 patients were enrolled. The median age was 73 years (range, 43-86), and 35 patients (72%) were women.EGFR mutation subtypes included exon 19 deletion (54%) and Leu858Arg point mutation (46%). Most patients had a performance status of 0 or 1 (91%) and a histological diagnosis of adenocarcinoma (98%). As of the data cut-off date of June 2017, the median follow-up was 18.9 months. The median PFS was 15.2 months (95% CI: 13.2-not estimable). The 1-year overall survival rate was 95.6% (95% CI: 89.7%-100%). The objective response rate was 81.8% (95% CI, 81.3%-98.6%). Adverse events of grade 3 or higher occurred in 14 patients (30.4%) and included rash/acne in 4 patients (8.7%), paronychia in 4 patients (8.7%), diarrhea in 2 patients (4.3%). There was no treatment-related death. CONCLUSIONS: Low starting dose of afatinib therapy showed promising clinical efficacy and good tolerability. Further investigations are warranted.
OBJECTIVES:Afatinib is an effective treatment in patients who have epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), but its toxicities often require dose adjustment. Exploratory analyses of previous trials have suggested that reducing the dose of afatinib can decrease treatment-related adverse events without negatively affecting effectiveness. The aim of this study was to assess the efficacy and safety of low starting dose of afatinib with dose modification according to its toxicity in patients with EGFR mutation-positive NSCLC. MATERIALS AND METHODS: This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib starting in a dose of 20 mg/day. If tolerated, the dose was increased in 10-mg increments up to 50 mg/day. The primary endpoint was progression-free survival (PFS). RESULTS: From February 2015 through March 2016, 46 patients were enrolled. The median age was 73 years (range, 43-86), and 35 patients (72%) were women.EGFR mutation subtypes included exon 19 deletion (54%) and Leu858Arg point mutation (46%). Most patients had a performance status of 0 or 1 (91%) and a histological diagnosis of adenocarcinoma (98%). As of the data cut-off date of June 2017, the median follow-up was 18.9 months. The median PFS was 15.2 months (95% CI: 13.2-not estimable). The 1-year overall survival rate was 95.6% (95% CI: 89.7%-100%). The objective response rate was 81.8% (95% CI, 81.3%-98.6%). Adverse events of grade 3 or higher occurred in 14 patients (30.4%) and included rash/acne in 4 patients (8.7%), paronychia in 4 patients (8.7%), diarrhea in 2 patients (4.3%). There was no treatment-related death. CONCLUSIONS: Low starting dose of afatinib therapy showed promising clinical efficacy and good tolerability. Further investigations are warranted.
Authors: René J Boosman; Jacobus A Burgers; Egbert F Smit; Neeltje Steeghs; Anthonie J van der Wekken; Jos H Beijnen; Alwin D R Huitema; Rob Ter Heine Journal: Drugs Date: 2021-12-11 Impact factor: 9.546
Authors: Ashley M Hopkins; Bradley D Menz; Michael D Wiese; Ganessan Kichenadasse; Howard Gurney; Ross A McKinnon; Andrew Rowland; Michael J Sorich Journal: Pharmacol Res Perspect Date: 2020-08
Authors: Mingjun Rui; Zijing Wang; Zhengyang Fei; Yao Wu; Yingcheng Wang; Lei Sun; Ye Shang; Hongchao Li Journal: Front Pharmacol Date: 2022-03-16 Impact factor: 5.810