Phase II Trial of Afatinib in Elderly Patients over 75 Years of Age with EGFR mutation positive NSCLC

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Anticancer Agents
Personalised/Precision Medicine
Geriatric Oncology
Presenter Yoshiro Nakahara
Citation Annals of Oncology (2018) 29 (suppl_9): ix150-ix169. 10.1093/annonc/mdy425
Authors Y. Nakahara1, S. Oizumi2, H. Mizugaki3, Y. Fujita4, T. Harada5, T. Takashina6, R. Ko7, K. Watanabe8, T. Hotta9, H. Minemura10, S. Saeki11, S. Yagishita12, A. Hamada12
  • 1Department Of Respiratory Medicine, Kitasato University School of Medicine, 252-0374 - Sagamihara/JP
  • 2Department Of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo/JP
  • 3First Department Of Medicine, Hokkaido University Hospital, Sapporo/JP
  • 4Department Of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, Asahikawa/JP
  • 5Center For Respiratory Diseases, JCHO Hokkaido Hospital, 062-8618 - Sapporo/JP
  • 6Department Of Respiratory Medicine, Iwamizawa Municipal General Hospital, Iwamizawa/JP
  • 7Department Of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo/JP
  • 8Department Of Thoracic Oncology And Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 113-0021 - Tokyo/JP
  • 9Department Of Internal Medicine, Division Of Medical Oncology And Respiratory Medicine, Shimane University Faculty of Medicine, Izumo/JP
  • 10Pulmonary Medicine, Fukushima Medical University, 960-1295 - Fukushima/JP
  • 11Respiratory Medicine, Kumamoto University Hospital, 860-8556 - Kumamoto city/JP
  • 12Division Of Molecular Pharmacology, National Cancer Center Research Institute, Tokyo/JP



Although reports on the use of gefitinib and erlotinib in elderly patients are occasionally found, reports on afatinib are rare. According to the analysis of Japanese patients in the LUX-Lung3 study, a dose reduction, from an initial dose of 40 mg/day, was necessary in 76.0% of the 54 patients in the afatinib group. However, prolonged administration was possible after dose reduction to 20 mg/day, and antitumor effects were maintained with the reduced dose.


The efficacy and safety of afatinib at 30 mg/day in PS0-1 patients who were over 75 years of age with EGFR mutation positive non-small cell lung cancer were studied. The primary endpoint was the response rate, and the planned number of registered cases was set at 35, with a threshold response rate of 50%, expected response rate of 75%, α of 0.05, and β of 0.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), incidence rate of adverse events (AE), quality of life (QOL) survey, and trough plasma concentration of afatinib at steady state (PK, collected between 8th to 15th day of oral administration).


The data of 35 patients were collected from May 2015 to August 2017. Patient background was, median age of 79 years (75-92), male/female: 8/27, PS 0/1: 8/27, adenocarcinoma/non-small cell cancer: 30/5, IIIA/IIIB/IV/postoperative recurrence (TNM 7th edition): 2/2/22/9, and exon19del/exon21L858R/exon19del+exon21L858R: 15/19/1. The best overall efficacy was PR/SD/PD/NE: 28/4/1/2, and the response rate was 80.0% (95% CI, 63.1-91.6). The median PFS was 14.0 months (95% CI, 11.8-22.4). The main AEs were rash 69%, diarrhea 60%, paronychia 51%, stomatitis 49%, anemia 37%, loss of appetite 23%, thrombocytopenia 23%, and fatigue 20%. While the treatments were initiated with afatinib at 30 mg, nine (26%) patients continued with 30 mg, 23 (66%) were reduced to 20 mg, and three (8%) discontinued treatment due to AEs (2 cases of drug-induced pneumonia and 1 of stomatitis). Treatment-related death was not observed.


Afatinib at 30 mg/day could be an effective treatment option for elderly patients, over 75 years of age, with good PS. This study also reported OS, PK, and QOL in detail. (UMIN 0000177050).

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Hokkaido University.


Boehringer Ingelheim, AMED16ck0106112h003.


Y. Nakahara: Honoraria: AstraZeneca, Eli Lilly, Bristol-Myers Squibb, Ono Pharmaceutical, Taiho; Pharmaceutical research Funding Eli Lilly. S. Oizumi: Honoraria: AstraZeneca, Eli Lilly; Research Funding Bristol-Myers Squibb, Kyowa Hakko Kirin, Merck Serono, Ono Pharmaceutical, Pfizer. H. Mizugaki: Honoraria: AstraZeneca, Boehringer Ingelheim, MSD, Chugai Pharmaceutical; Research Funding Boehringer Ingelheim. All other authors have declared no conflicts of interest.