Keunchil Park1, Jin-Soo Kim2, Joo-Hang Kim3, Young-Chul Kim4, Hoon-Gu Kim5, Eun Kyung Cho6, Jong-Youl Jin7, Miyoung Kim8, Angela Märten9, Jin-Hyoung Kang10. 1. Division of Hematology-Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351, Seoul, South Korea. kpark@skku.edu. 2. Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea. 3. CHA Bundang Medical Center, CHA University, Gyeonggi-do, Seongnam, South Korea. 4. Chonnam National University Medical School, CNU Hwasun Hospital, Gwangju, South Korea. 5. Department of Internal Medicine, Gyeongsang National University College of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea. 6. Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea. 7. Bucheon St Mary's Hospital, The Catholic University of Korea, Bucheon, South Korea. 8. Boehringer Ingelheim Korea Ltd, Seoul, South Korea. 9. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. 10. Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Abstract
BACKGROUND: Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its 'real-world' safety and efficacy. METHODS: EGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms. RESULTS: Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9-23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4-21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34-66%/36-66%/0-3% of patients over the first year. CONCLUSIONS: No unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations. TRIALS REGISTRATION: ClinicalTrials.gov NCT01931306 ; 29/08/2013.
BACKGROUND:Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its 'real-world' safety and efficacy. METHODS:EGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms. RESULTS: Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9-23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4-21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34-66%/36-66%/0-3% of patients over the first year. CONCLUSIONS: No unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations. TRIALS REGISTRATION: ClinicalTrials.gov NCT01931306 ; 29/08/2013.
Authors: Sung Yong Lee; Chang-Min Choi; Yoon Soo Chang; Kye Young Lee; Seung Joon Kim; Sei Hoon Yang; Jeong Seon Ryu; Jeong Eun Lee; Shin Yup Lee; Ji Young Park; Young-Chul Kim; In-Jae Oh; Chi Young Jung; Sang Hoon Lee; Seong Hoon Yoon; Juwhan Choi; Tae Won Jang Journal: Transl Lung Cancer Res Date: 2021-12