Abstract 3998: Phase II trial of afatinib in elderly patients over 75 years of age withEGFR mutation positive non-small cell lung cancer
Authors: Watanabe Kageaki , Oizumi Satoshi , Mizugaki Hidenori , Fujita Yuka , Harada Toshiyuki , Takashina Taichi , Igawa Satoshi , Ko Ryo , Hotta Takamasa , Minemura Hiroyuki , Saeki Sho , Yagishita Shigehiro , Hamada Akinobu 
Published: August 2019

Abstract
Background: 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 54 Japanese patients in the LUX-Lung3 study, an afatinib dose reduction from 40 mg/day, was necessary for 76.0%. However, the prolonged administration was possible after a dose reduction to 20 mg/day, and antitumor effects were maintained with the reduced dose.
Material and methods: 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 (RR), and the planned number of registered cases was set at 35, with a threshold RR of 50%, an expected RR of 75%, α of 0.05, and β of 0.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), the incidence rate of adverse events (AE), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady state (PK, collected between 8th to 15th day of oral administration).
Results: 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/NSCLC: 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 RR was 80.0% (95% CI, 63.1-91.6). The median PFS and OS were 16.3 months (95% CI, 11.8-27.0) and not reached. The main AEs were rash 69%, diarrhea 60%, and paronychia 51%. While the initial afatinib dose was 30 mg, nine (26%) patients continued with 30 mg, 23 (66%) were reduced to 20 mg, and three (8%) discontinued due to AEs (2 ILD and 1 stomatitis). Treatment-related death was not observed. There is no significant change of QOL at baseline, after 4, 8, and 12 weeks. PK analyses showed steady state plasma concentration as 22.8 ng/mL which was comparable to reported plasma concentration of 40 mg afatinib in LUX-LUNG3 and 6 trials (24.3 ng/mL). No obvious PK differences were found according to dose reduction, adverse event, and response.
Conclusions: Afatinib at 30 mg/day could be an effective treatment option for elderly patients, over 75 years of age, with good PS. (UMIN 0000177050)
Citation Format: Kageaki Watanabe, Satoshi Oizumi, Hidenori Mizugaki, Yuka Fujita, Toshiyuki Harada, Taichi Takashina, Satoshi Igawa, Ryo Ko, Takamasa Hotta, Hiroyuki Minemura, Sho Saeki, Shigehiro Yagishita, Akinobu Hamada. Phase II trial of afatinib in elderly patients over 75 years of age withEGFR mutation positive non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3998.