Although EGFR-TKI alone has been a standard first-line treatment for pts with advanced NSCLC with EGFR mutations, our phase II study (NEJ005) showed promising efficacy of GCP. NEJ009, an open-label, randomized phase III study, was conducted to evaluate the superiority of GCP vs G in progression-free survival (PFS), PFS2, and overall survival (OS).
Pts with newly diagnosed stage III/IV/recurrent NSCLC harboring EGFR activating mutations (exon 19 deletion or exon 21 L858R) were randomized 1:1 to G 250 mg PO QD or GCP (G 250mg PO QD combined with carboplatin AUC 5 + pemetrexed 500mg/m2, every 3 weeks). The primary endpoints consisting of PFS, PFS2, and OS were sequentially analyzed according to a preplanned gate-keeping method. Secondary endpoints included objective response rate, safety, and quality of life.
From Oct 2011 to Sep 215, 345 pts were enrolled and 342 pts (G 172, GCP 170) were evaluated. Baseline characteristics fairly well balanced between the arms. GCP demonstrated significantly better PFS compared to G as below. Although there was no difference in PFS2 between the arms, additional OS analysis (G 101 events vs GCP 83 events) revealed that median survival time of GCP was much longer than that of G (52.2 months vs 38.8 months, HR: 0.695, p = 0.013). Details of post-protocol treatments in both arms will be presented at the meeting.
NEJ009 was the first phase III study which evaluated the efficacy of a combination of EGFR-TKI and platinum doublet chemotherapy in untreated advanced NSCLC pts with EGFR mutations. Although GCP regimen failed to demonstrate its superiority in PFS2, it increased long survivors.Table: 1382PD
|ITT population||GCP (N = 169)||G (N = 172)|
|Median (months)||Median (months)||HR|
|95%CI:18.0, 24.2||95%CI:9.0,13.4||95%CI:0.390, 0.623|
|P < 0.001|
|P = 0.806|
|OS (additional analysis)||52.2||38.8||0.695 (P = 0.013)|
Clinical trial identification
Legal entity responsible for the study
North East Japan Study Group (NEJ).
Has not received any funding.
M. Seike: Lecture fees: AstraZeneca, Eli Lilly, Taiho Pharmaceutical. A. Inoue: Lecture fees: AstraZeneca, Eli Lilly, Boehringer Ingelheim, MSD, Chugai, Pfizer. S. Sugawara: Lecture fees: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Eli Lilly and Company, Novartis, Kyowa Hakko Kirin, Bristol-Myers Squibb, Ono Pharmaceutical, MSD K.K. S. Morita: Lecture fees: AstraZeneca, Eli Lilly. Y. Hosomi: Lecture fees: AstraZeneca, Taiho Pharmaceutical, Lilly, Chugai Phama, Ono Taiho Pharmaceutical, Bristol-Myers Squibb Japan, MSD. K. Takahashi: Lecture fees and research funding: AstraZeneca, Eli Lilly. Y. Fujita: Lecture fees: Chugai, Ono, Eli Lilly; Research funding: Taiho, Chugai, Eli Lilly, Pfizer Japan. K. Minato: Research funding: Taiho, Bristol-Myers Squibb, Quintiles. K. Kobayashi: Lecture fees: AstraZeneca, Chugai, Ono, Eli Lilly; Consulting or advisory role fee: AstraZeneca. T. Nukiwa: Lecture fees: Asahi-Kasei, Nippon Boehringer Ingelheim. All other authors have declared no conflicts of interest.