Yun Fan1, Jianhua Chen2, Chengzhi Zhou3, Huijuan Wang4, Yongqian Shu5, Jacky Zhang6, Hairui Hua6, Dennis Chin-Lun Huang7, Caicun Zhou8. 1. Zhejiang Cancer Hospital, Hangzhou, China. 2. Hunan Cancer Hospital, Changsha, China. 3. The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China. 4. Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China. 5. The First Affiliated Hospital with Nanjing Medical University, Jiangsu, China. 6. Boehringer Ingelheim (China) Investment Co., Ltd, Shanghai, China. 7. Boehringer Ingelheim Taiwan Limited, Taipei, Taiwan. 8. Medical Oncology, Shanghai Pulmonary Hospital, Shanghai, China. Electronic address: caicunzhoudr@163.com.
Abstract
BACKGROUND: Despite 1-4 % of NSCLC tumors harboring mutations in the HER2 gene, there are no approved HER2-pathway-targeted treatments available. We report an open-label, single-arm, multicenter phase II study investigating the efficacy and safety of afatinib in Asian patients with HER2-mutation positive (HER2m+) NSCLC. METHODS: Eligible patients for Part A had confirmed stage IIIb/IV HER2m + NSCLC, had failed one or two prior lines of chemotherapy, and were EGFR/HER2-inhibitor naïve. Patients received oral afatinib 40 mg/day in continuous 28-day cycles, until disease progression or intolerable adverse events (AEs). Patients qualified for Part B if they had > 12 weeks' clinical benefit and Eastern Cooperative Oncology Group performance status ≤ 2. In Part B, patients were to receive afatinib at the last received dose, plus paclitaxel 80 mg/m2 weekly, until disease progression or intolerable AEs. The primary endpoint in Part A was objective response (OR); secondary endpoints included disease control (DC), progression-free survival (PFS), and overall survival (OS). Further exploratory endpoints were OR, DC, and PFS in Part B. RESULTS: Eighteen patients received afatinib in Part A. No patient achieved an OR; 11 patients (61.1 %) achieved stable disease, and six patients (33.3 %) had progressive disease. DC rate was therefore 61.1 % (95 % confidence interval [CI]: 35.7, 82.7). A decrease in tumor size from baseline of > 0 to < 30 % was observed in eight patients. At the time of analysis, 16 patients (88.9 %) had progressed or died. Median PFS was 2.76 months (95 % CI: 1.87, 4.60) and median OS was 10.02 months (95 % CI: 8.47, 10.08). All patients experienced ≥ 1 AE, most commonly diarrhea (66.7 %) and rash (33.3 %). No patients met the inclusion criteria for Part B, and recruitment was slow; therefore, the study was terminated. CONCLUSIONS: This study found no clinical benefit of afatinib for EGFR TKI-naïve patients with HER2m + NSCLC.
BACKGROUND: Despite 1-4 % of NSCLC tumors harboring mutations in the HER2 gene, there are no approved HER2-pathway-targeted treatments available. We report an open-label, single-arm, multicenter phase II study investigating the efficacy and safety of afatinib in Asian patients with HER2-mutation positive (HER2m+) NSCLC. METHODS: Eligible patients for Part A had confirmed stage IIIb/IV HER2m + NSCLC, had failed one or two prior lines of chemotherapy, and were EGFR/HER2-inhibitor naïve. Patients received oral afatinib 40 mg/day in continuous 28-day cycles, until disease progression or intolerable adverse events (AEs). Patients qualified for Part B if they had > 12 weeks' clinical benefit and Eastern Cooperative Oncology Group performance status ≤ 2. In Part B, patients were to receive afatinib at the last received dose, plus paclitaxel 80 mg/m2 weekly, until disease progression or intolerable AEs. The primary endpoint in Part A was objective response (OR); secondary endpoints included disease control (DC), progression-free survival (PFS), and overall survival (OS). Further exploratory endpoints were OR, DC, and PFS in Part B. RESULTS: Eighteen patients received afatinib in Part A. No patient achieved an OR; 11 patients (61.1 %) achieved stable disease, and six patients (33.3 %) had progressive disease. DC rate was therefore 61.1 % (95 % confidence interval [CI]: 35.7, 82.7). A decrease in tumor size from baseline of > 0 to < 30 % was observed in eight patients. At the time of analysis, 16 patients (88.9 %) had progressed or died. Median PFS was 2.76 months (95 % CI: 1.87, 4.60) and median OS was 10.02 months (95 % CI: 8.47, 10.08). All patients experienced ≥ 1 AE, most commonly diarrhea (66.7 %) and rash (33.3 %). No patients met the inclusion criteria for Part B, and recruitment was slow; therefore, the study was terminated. CONCLUSIONS: This study found no clinical benefit of afatinib for EGFR TKI-naïve patients with HER2m + NSCLC.
Authors: Bob T Li; Egbert F Smit; Yasushi Goto; Kazuhiko Nakagawa; Hibiki Udagawa; Julien Mazières; Misako Nagasaka; Lyudmila Bazhenova; Andreas N Saltos; Enriqueta Felip; Jose M Pacheco; Maurice Pérol; Luis Paz-Ares; Kapil Saxena; Ryota Shiga; Yingkai Cheng; Suddhasatta Acharyya; Patrik Vitazka; Javad Shahidi; David Planchard; Pasi A Jänne Journal: N Engl J Med Date: 2021-09-18 Impact factor: 176.079