Abstract 680P
Background
The global observational study (Gio-Tag) demonstrated prolonged time on treatment (ToT) with sequential AFA followed by OSI post detection of T790M in EGFR-mutant NSCLC. Gio-Tag Japan, a prospective study of real-world data (RWD) showed reproducibility of favorable results by this sequence strategy. AFA is occasionally prescribed under initial dose reduction in elderly or poor general status patients (pts), we thus investigated clinical outcomes according to initial AFA dosages.
Methods
This study is an exploratory analysis of multicentre prospective observational study, Gio-Tag Japan. We evaluated clinical courses of EGFR-mutant NSCLC pts who had received first-line AFA. Primary endpoint was ToT: duration of sequential AFA to OSI.
Results
From September 2019 to July 2020, 121 pts were enrolled from 64 participating institutions in Japan. Total 119 cases were evaluated, except two ineligible cases. Median age was 72 (range, 38-94), including 45 males and 74 females. All pts were ECOG PS 0-1. Del-19 mutations were identified in 52 pts and L858R in 67. The initial AFA dosage was as follows: 20mg/30mg/40mg in 14 (12%)/ 43 (36%)/ 62 (52%), respectively. Main reasons for dose adjustment were elderly age (55%) and toxicity concern (35%). Total median progression-free survival (mPFS) of AFA was 18.4 (95%CI, 13.1-21.7) months. mPFSs of AFA 20mg, 30mg, 40mg were 15.9 (95%CI, 2.5-23.8), 18.7 (95%CI, 13.1-25.1), 15.4 (95%CI, 11.0-23.7), months, respectively. Total median overall survival (mOS) was 45.6 (95%CI, 37.3-not reached [NR]) months. mOSs of AFA 20mg, 30mg, 40mg were 38.9 (95%CI, 7.0-45.6), NR (95%CI, 39.1-NR), 40.8 (95%CI, 27.5-NR) months, respectively. mToT in 29 pts receiving sequential AFA to OSI was 31.8 (95%CI, 20.4-39.2) months. Those of AFA 20mg (n=2), 30mg (n=13), 40mg (n=14) were NR, 35.5 (95%CI, 19.8-NR), 31.8 (95%CI, 11.8-37.5) months, respectively.
Conclusions
30mg initial dose AFA suggested favorable PFS and OS, compared to 20mg and 40mg. Based on our RWD including relatively many elderly pts, 30mg initial dose AFA might be appropriate for elderly pts or those with toxicity concern.
Clinical trial identification
UMIN000037452.
Editorial acknowledgement
David Martin: a native English writer.
Legal entity responsible for the study
The authors.
Funding
Boehringer Ingelheim.
Disclosure
A. Hata: Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim, MSD, Chugai, AstraZenaca, Pfizer. T. Sumi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., AstraZeneca, Nippon Boehringer Ingelheim Co., Ltd. H. Yoshioka: Financial Interests, Personal, Invited Speaker, Lecture fee: Eli Lilly Japan K.K., Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, MSD, AstraZeneca, Ono Pharmaceutical, Novartis Pharma, Kyowa Kirin, Otsuka Pharmaceutical, Amgen, Pfizer, Daiichi Sankyo, Nipro Pharma, Merck Biopharma; Financial Interests, Personal, Other, Consulting fee: Delta-Fly Pharma, Inc.; Financial Interests, Institutional, Local PI: Daiichi Sankyo, AstraZeneca, Jannsen Pharmaceutical, MSD, Novartis Pharma; Financial Interests, Institutional, Coordinating PI: Delta-Fly Pharma, Boehringer Ingelheim. K. Sakai: Financial Interests, Personal, Invited Speaker: Qiagen, Inc., Takeda Pharmaceutical Co., Ltd., Nippon Kayaku Co.,Ltd. K. Nishio: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Chugai Pharmaceutical CO.,LTD., Novartis Pharma K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Daiichi Sankyo, Invitae Japan, Nichirei Biosciences Inc., Maruho Co., Ltd.; Financial Interests, Personal, Advisory Board: Otsuka Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Limited., Guardant Health Inc., Janssen Pharmaceutical; Financial Interests, Personal, Research Grant: West Japan Oncology Group, Nichirei Biosciences Inc., Hitachi, Ltd., osakaminami hospital, Sysmex Corporation, Otsuka Pharmaceutical, Thoracic Oncology Research Group, University Public Corporation Osaka. N. Katakami: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda Pharmaceutical, Chugai Pharmaceutical, Kyorin Pharmaceutical, Bristol Myer Squib, Ono Pharmaceutical, Boheringer Ingelheim, Kyowa-Kirin, Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Local PI: Chugai Pharmaceutical. All other authors have declared no conflicts of interest.