Moon Ki Choi1, Jin Seok Ahn2, Young-Chul Kim3, Byoung Chul Cho4, In-Jae Oh3, Sang-We Kim5, Jong Seok Lee6, Joo-Hang Kim4, Myung-Ju Ahn2, Keunchil Park7. 1. Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea. 2. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 3. Department of Internal Medicine, Chonnam National University Hwasun Hospital, Jeonnam, Republic of Korea. 4. Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. 5. Department of Oncology, Asan Medical Cancer, University of Ulsan College of Medicine, Seoul, Republic of Korea. 6. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea. 7. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: kpark@skku.edu.
Abstract
INTRODUCTION: Afatinib, an irreversible ErbB family blocker, approved for first-line treatment of epidermal growth factor receptor (EGFR) mutated advanced non-small cell lung cancer (NSCLC). This study investigated experience of afatinib within a compassionate use program (CUP). METHODS: The afatinib CUP was an open-label, multicenter, single-arm program in Korea. We enrolled patients with stage IV NSCLC and who had received at least one line of previous cytotoxic chemotherapy and previous EGFR TKI treatment with either an EGFR mutation or documented clinical benefit. The starting dose of afatinib was 50 mg once daily. RESULTS: From August 2011 to September 2014, 332 patients received at least one dose of afatinib. Most patients were registered in the CUP for fourth- or fifth-line treatment with afatinib. Adverse events (AEs) occurred in 98.1% of patients, including 29.8% with serious AEs. The most common AEs (all grades) were diarrhea (90.1%) and skin rash (62.0%). Dose reductions occurred in 60.5% of patients and discontinuations due to AEs were reported in 11.1% of patients. The response rate and median time to treatment failure (TTF) were 27.4% and 3.3 months (CI 95%, 2.8-3.8 months), respectively, in this highly pretreated population. In subgroup analysis, ECOG PS 0 or 1 and immediate pretreatment with pemetrexed monotherapy or a platinum doublet were associated with a longer TTF for afatinib. CONCLUSIONS: No additional or unexpected safety concerns were observed, and afatinib demonstrated moderate antitumor activity in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib in a real-world setting.
INTRODUCTION:Afatinib, an irreversible ErbB family blocker, approved for first-line treatment of epidermal growth factor receptor (EGFR) mutated advanced non-small cell lung cancer (NSCLC). This study investigated experience of afatinib within a compassionate use program (CUP). METHODS: The afatinib CUP was an open-label, multicenter, single-arm program in Korea. We enrolled patients with stage IV NSCLC and who had received at least one line of previous cytotoxic chemotherapy and previous EGFR TKI treatment with either an EGFR mutation or documented clinical benefit. The starting dose of afatinib was 50 mg once daily. RESULTS: From August 2011 to September 2014, 332 patients received at least one dose of afatinib. Most patients were registered in the CUP for fourth- or fifth-line treatment with afatinib. Adverse events (AEs) occurred in 98.1% of patients, including 29.8% with serious AEs. The most common AEs (all grades) were diarrhea (90.1%) and skin rash (62.0%). Dose reductions occurred in 60.5% of patients and discontinuations due to AEs were reported in 11.1% of patients. The response rate and median time to treatment failure (TTF) were 27.4% and 3.3 months (CI 95%, 2.8-3.8 months), respectively, in this highly pretreated population. In subgroup analysis, ECOG PS 0 or 1 and immediate pretreatment with pemetrexed monotherapy or a platinum doublet were associated with a longer TTF for afatinib. CONCLUSIONS: No additional or unexpected safety concerns were observed, and afatinib demonstrated moderate antitumor activity in advanced NSCLCpatients with acquired resistance to gefitinib or erlotinib in a real-world setting.