PMID- 34253172 OWN - NLM STAT- MEDLINE DCOM- 20211101 LR - 20240402 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 21 IP - 1 DP - 2021 Jul 12 TI - An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naive patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations. PG - 802 LID - 10.1186/s12885-021-08445-9 [doi] LID - 802 AB - BACKGROUND: Afatinib is approved globally for EGFR-TKI treatment-naive 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-naive 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. CI - (c) 2021. The Author(s). FAU - Park, Keunchil AU - Park K AD - 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. FAU - Kim, Jin-Soo AU - Kim JS AD - Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea. FAU - Kim, Joo-Hang AU - Kim JH AD - CHA Bundang Medical Center, CHA University, Gyeonggi-do, Seongnam, South Korea. FAU - Kim, Young-Chul AU - Kim YC AD - Chonnam National University Medical School, CNU Hwasun Hospital, Gwangju, South Korea. FAU - Kim, Hoon-Gu AU - Kim HG AD - Department of Internal Medicine, Gyeongsang National University College of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea. FAU - Cho, Eun Kyung AU - Cho EK AD - Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea. FAU - Jin, Jong-Youl AU - Jin JY AD - Bucheon St Mary's Hospital, The Catholic University of Korea, Bucheon, South Korea. FAU - Kim, Miyoung AU - Kim M AD - Boehringer Ingelheim Korea Ltd, Seoul, South Korea. FAU - Marten, Angela AU - Marten A AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Kang, Jin-Hyoung AU - Kang JH AD - Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. LA - eng SI - ClinicalTrials.gov/NCT01931306 PT - Journal Article DEP - 20210712 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Protein Kinase Inhibitors) RN - 41UD74L59M (Afatinib) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adult MH - Afatinib/pharmacology/*therapeutic use MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology MH - ErbB Receptors/*genetics MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/pathology MH - Male MH - Middle Aged MH - Mutation MH - Protein Kinase Inhibitors/pharmacology/*therapeutic use PMC - PMC8274031 OTO - NOTNLM OT - Afatinib OT - Brain metastases OT - EGFR OT - NSCLC OT - Real world OT - Uncommon mutations COIS- KP has received personal fees from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Eli Lilly, Hanmi, Kyowa Hakko Kirin, Incyte, LOXO, Merck KGaA, Merck Sharp & Dohme, Ono, Novartis, and Roche; and research funding from AstraZeneca and Merck Sharp & Dohme. YCK reports grants from Boehringer Ingelheim and AstraZeneca, outside the submitted work. MK and AM are employees of Boehringer Ingelheim. JHK reports personal fees from Boehringer Ingelheim, grants from AstraZeneca, Ono, CKD, and Astellas, grants and personal fees from YooHan, and personal fees from Merck Sharp & Dohme outside the submitted work. All other authors declare that they have no competing interests. EDAT- 2021/07/14 06:00 MHDA- 2021/11/03 06:00 PMCR- 2021/07/12 CRDT- 2021/07/13 05:34 PHST- 2021/01/13 00:00 [received] PHST- 2021/05/28 00:00 [accepted] PHST- 2021/07/13 05:34 [entrez] PHST- 2021/07/14 06:00 [pubmed] PHST- 2021/11/03 06:00 [medline] PHST- 2021/07/12 00:00 [pmc-release] AID - 10.1186/s12885-021-08445-9 [pii] AID - 8445 [pii] AID - 10.1186/s12885-021-08445-9 [doi] PST - epublish SO - BMC Cancer. 2021 Jul 12;21(1):802. doi: 10.1186/s12885-021-08445-9.