1267P - Sequential afatinib (AFA) to osimertinib (OSI) in EGFR-mutant NSCLC: Primary analysis of Gio-Tag Japan, a multicenter prospective observational study

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. However, real world data (RWD) on this sequence strategy has not been fully evaluated in Japan.

Methods

This study is a multicentre prospective observational study. We evaluated clinical courses of EGFR-mutant NSCLC patients (pts) who had received first-line AFA. Primary endpoint was ToT: duration of sequential AFA to OSI (threshold/expected median ToT [mToT]: 23/34.5 months and α/1-β: one-sided 0.1/0.7).

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. One hundred and eight pts (91%) had adenocarcinoma, with 85 stage IV and 34 stage III/recurrence diseases. Del-19 mutations were identified in 52 pts and L858R in 67. The starting dose of AFA was as follows: 20mg/30mg/40mg in 14 (12%)/ 42 (35%)/ 63 (53%), respectively. Main reasons for dose adjustment were elderly age (55%) and toxicity concern (35%). mToT in 29 pts receiving sequential AFA to OSI was 31.8 (80%/95%CI, 24.3-37.0/20.4-38.2) months, representing a statistical positivity. Second-line OSI was introduced in 29 (31%) of 98 pts after AFA failure. mOS in these pts was not reached, and 3-year OS rate was 67%. mOS of total study population was 45.6 (95%CI, 37.3-not reached) months. mPFS/mTTF of AFA was 18.4/15.1 (95%CI, 13.1-21.7/11.5-20.6) months. mPFS/mTTF of OSI was 6.7/7.9 (95%CI, 4.3-23.0/5.5-17.0) months. Among 29 pts receiving sequential AFA to OSI, mToT were 33.6 (95%CI, 23.3-39.2) months in Del-19 (n=20), and 20.4 (95%CI, 5.8-39.9) months in L858R (n=9).

Conclusions

Japanese RWD of sequential AFA to OSI demonstrated comparable mToT and mOS to the results on global Gio-Tag study. Sequential strategy of AFA to OSI could prolong continuous TKI duration and prognosis in a part of pts with EGFR-mutant NSCLC.

Clinical trial identification

UMIN000037452.

Editorial acknowledgement

Legal entity responsible for the study

Nobuyuki Katakami.

Funding

Boehringer Ingelheim company.

Disclosure

N. Takase: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Bristol Myers Squibb, Takeda pharmaceuticals, Taiho Pharmaceuticals, AstraZeneca, Eisai Company, Chugai pharmaceuticals, Merck KGaA, MSD, Nippon Kayaku Company, Kyowakirin; Financial Interests, Institutional, Research Funding: Delta-Fly pharma, MSD, AbbVie. A. Hata: Financial Interests, Institutional, Research Funding: MSD, Eli Lilly, Chugai, Taiho, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly, MSD, Chugai, Pfizer, AstraZeneca, Boehringer Ingelheim, Taiho Pharmaceuticals. 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, Janssen Pharmaceutical, MSD, Novartis Pharma; Financial Interests, Institutional, Coordinating PI: Delta-Fly Pharma, Boehringer Ingelheim. Y. Fujisaka: Financial Interests, Institutional, Research Funding: MSD, Taiho Pharmaceuticals, Regeneron, Ono Pharmaceuticals, Bristol Myers Squibb, Merck; Financial Interests, Personal, Invited Speaker: Eli Lilly, MSD, Chugai pharmaceuticals, Pfizer, AstraZeneca, Boehringer Ingelheim, Taiho Pharmaceuticals, Eisai company. T. Ota: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Daiichi Sankyo, Taiho. M. Mitsui: Financial Interests, Institutional, Research Funding: Chugai pharmaceuticals; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono Pharmaceuticals, Chugai pharmaceuticals, Japan blood Products Organization, CSL Behring. R. Morita: Financial Interests, Personal, Invited Speaker: Eli Lilly, MSD, Chugai, Pfizer, AstraZeneca, Daiichi Sankyo, Taiho Pharmaceuticals, Novartis, Bristol Myers Squibb. S. Morita: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai pharmaceuticals, Eli Lilly, MSD, Ono Pharmaceuticals. 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, Boehringer 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.