We constructed a data set of EGFR-mutant NSCLC patients (pts) and compared the overall survival of first-generation (1G) and second-generation (2G) EGFR-TKIs in clinical practice using propensity score.
We reviewed the available data of all EGFR-mutated NSCLC pts who received EGFR-TKI therapy between Jan 2008 and Aug 2017 in the 11 institutions in Japan. The primary endpoint was OS. When comparing OS between 1G and 2G EGFR-TKIs, the propensity scoring was performed using two methods; matching and IPTW with adjusted factors (age, sex, smoking history, histology, EGFR mutational subtype, clinical stage, ECOG PS, line of treatment, brain metastasis) which were previously described in the statistical plan. The statistical plan had been opened prior to statistical analysis. (Clinical Trial information: UMIN000030121)
A total of 1400 pts from 11 institutions were enrolled in this study, and the data from the 1354 pts who received EGFR-TKI alone was analyzed (gefitinib, N = 726; erlotinib, N = 413; afatinib, N = 215). Median age was 70, [range, 28-99] and 61.3% were female. The mutational status was exon 19 deletion in 671 pts, L858R in 571 pts, and minor or compound mutation in 112 pts. 95.1% were histologically diagnosed with adenocarcinoma, and 81.1% were with 0 to 1 of ECOG PS. Median OS (months [95%CI]) were 30.9 [27.7-33.9] in 1G (gefitinib, 32.2 [28.4-36.4]; erlotinib, 28.1 [24.9-33.4]), and 38.6 [32.2-NR] in 2G (afatinib), respectively. The trend of longer OS for afatinib against first-generation EGFR-TKIs remained even after adjusted by propensity score. (unadjusted, HR 0.682, p = 0.0031; adjusted by IPTW, HR 0.783 p < 0.0001; adjusted by matching [1:2], HR 0.747, p = 0.0629) Subgroup analysis showed that the patients with exon 19 deletion had significantly longer overall survival benefit from afatinib therapy than 1G EGFR-TKI. (vs. gefitinib, p = 0.0016; vs. erlotinib, p = 0.0135).
From this analysis of 1354 data records, using propensity scoring, afatinib had a trend of longer OS compared with gefitinib and erlotinib.
Clinical trial identification
Legal entity responsible for the study
Aichi Cancer Center Hospital.
K. Ito: Research funding: Boehringer Ingelheim, Chugai Pharmaceutical Co, Novartis, GlaxoSmithKline, Daiichi Sankyo, Ono Pharmaceutical Co; Honoraria: Boehringer Ingelheim, Chugai Pharmaceutical Co, Eli Lily, Ono Pharmaceutical Co, MSD, AstraZeneca. A. Kubo: Honoraria: Chugai Pharma, Boehringer Ingelheim, Taiho Pharmaceutical, AstraZeneca, Novartis, Eli Lilly; Research Funding: Chugai Pharma, Boehringer Ingelheim, Eli Lilly. H. Taniguchi: Lecture Fees: AstraZeneca, Ono Pharm, Daiichi Sankyo, Chugai Pharm, Boehringer Ingelheim, Kyowa Hakko Kirin Co, Otsuska Pharm. K. Imaizumi: Research Funding: Taiho Pharm, Boehringer Ingelheim; Honoraria: Boehringer Ingelheim, Chugai Pharm, AstraZeneca, Ono Pharm, MSD, Eli Lilly. O. Hataji: Lecture Fees: Novartis, Boehringer Ingelheim; Research Fundings: Novartis, Boehringer Ingelheim, Kyorin Pharm, Bayer Health Care, Daiichi Sankyo, Glaxo Smith Kline. T. Yamaguchi: Honoraria: Boehringer Ingelheim, Chugai Pharm, AstraZeneca, Ono Pharm, MSD, Eli Lilly. Y. Oya: Honoraria: Boehringer Ingelheim, Chugai Pharm, AstraZeneca, Ono Pharm, MSD, Eli Lilly, T. Hida: Research fund: Boehringer Ingelheim, Chugai, Novartis, AstraZeneca, Pfizer, Astellas, Clovis Oncology, Taiho Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.