Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Nov 1;40(31):3587-3592.
doi: 10.1200/JCO.21.02911. Epub 2022 Aug 12.

Updated Analysis of NEJ009: Gefitinib-Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated EGFR

Eisaku Miyauchi  1 , Satoshi Morita  2 , Atsushi Nakamura  3 , Yukio Hosomi  4 , Kana Watanabe  5 , Satoshi Ikeda  6 , Masahiro Seike  7 , Yuka Fujita  8 , Koichi Minato  9 , Ryo Ko  10 , Toshiyuki Harada  11 , Koichi Hagiwara  12 , Kunihiko Kobayashi  13 , Toshihiro Nukiwa  14 , Akira Inoue  15 ; North-East Japan Study Group
Affiliations
Randomized Controlled Trial

Updated Analysis of NEJ009: Gefitinib-Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated EGFR

Eisaku Miyauchi et al. J Clin Oncol. .

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized, open-label, phase III NEJ009 study, gefitinib plus chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) compared with gefitinib-alone in patients with untreated non-small-cell lung cancer harboring mutations in epidermal growth factor receptor. Herein, we report the updated survival outcome and long-term tolerability. Patients were randomly assigned to gefitinib (gefitinib 250 mg orally, once daily) and gefitinib combined with carboplatin plus pemetrexed (GCP in a 3-week cycle for six cycles followed by concurrent gefitinib and pemetrexed maintenance) groups. At the data cutoff (May 22, 2020), GCP demonstrated significantly better PFS2 (hazard ratio, 0.77; 95% CI, 0.62 to 0.97; P = .027) than gefitinib. However, the updated median OS was 38.5 months (95% CI, 31.1 to 47.1) and 49.0 months (95% CI, 41.8 to 56.7) in the gefitinib and GCP groups, respectively (hazard ratio, 0.82; 95% CI, 0.64 to 1.06; P = .127). The OS in both groups was similar for the overall patient population. No severe adverse events occurred since the first report. This updated analysis revealed that the GCP regimen improved PFS and PFS2 with an acceptable safety profile compared with gefitinib-alone. GCP is more efficient than gefitinib monotherapy as a first-line treatment for non-small-cell lung cancer with epidermal growth factor receptor mutations.

PubMed Disclaimer

Conflict of interest statement

Eisaku MiyauchiHonoraria: AstraZeneca, Chugai Pharma, Boehringer Ingelheim, Ono Pharmaceutical, Lilly, Taiho Pharmaceutical, Kyowa Kirin, Novartis, Daiichi Sankyo, Bristol Myers Squibb, MerckConsulting or Advisory Role: Chugai Pharma, Boehringer Ingelheim, Lilly, Kyowa KirinResearch Funding: Boehringer Ingelheim, Lilly (Inst), Chugai Pharma (Inst) Satoshi MoritaHonoraria: AstraZeneca Japan, Bristol Myers Squibb Company, Chugai Pharma, Taiho Pharmaceutical, Lilly Japan, MSD K.K, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer Japan Inc, Eisai, Novartis, Kyowa Kirin Co LtdResearch Funding: Eisai (Inst) Atsushi NakamuraHonoraria: AstraZeneca, Chugai Pharma, Lilly Japan, Kyowa Kirin, Taiho Pharmaceutical, Novartis, Thermo Fisher Scientific Yukio HosomiSpeakers' Bureau: AstraZeneca, Taiho Pharmaceutical, Lilly Japan, Chugai Pharma, Ono Pharmaceutical, Bristol Myers Squibb Japan, MSD, Kyowa Kirin International Satoshi IkedaHonoraria: Chugai Pharma, Boehringer Ingelheim, Taiho Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Lilly, Pfizer, TakedaResearch Funding: Chugai Pharma, AstraZeneca Masahiro SeikeHonoraria: AstraZeneca, MSD K.K, Chugai Pharma, Taiho Pharmaceutical, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Nippon Boehringer Ingelheim, Novartis, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi-Sankyo CompanyResearch Funding: Taiho Pharmaceutical, Chugai Pharma, Lilly, MSD K.K, Nippon Boehringer Ingelheim, Nippon Kayaku Yuka FujitaResearch Funding: Novartis (Inst), Asahi Kasei (Inst), Ono Pharmaceutical (Inst), Otsuka (Inst), Lilly Japan (Inst) Koichi MinatoHonoraria: Bristol Myers Squibb Japan, Chugai PharmaResearch Funding: Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst) Ryo KoHonoraria: Taiho Pharmaceutical, Chugai Pharma, Lilly Japan, Boehringer Ingelheim, Pfizer, AstraZeneca, Ono Pharmaceutical, Daiichi Sankyo/UCB Japan, TakedaResearch Funding: MSD Koichi HagiwaraHonoraria: AstraZeneca, Chugai Pharma, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Novartis, Kyorin, Takeda, Lilly, Nippon Shinyaku, Kyowa Kirin, Nippon Kayaku, Bayer YakuhinResearch Funding: Ono Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim (Inst), Eiken ChemicalPatents, Royalties, Other Intellectual Property: LSI Medience Kunihiko KobayashiSpeakers' Bureau: AstraZeneca, Takeda Toshihiro NukiwaConsulting or Advisory Role: Nippon Boehringer Ingelheim, Grifols Akira InoueHonoraria: AstraZeneca, Boehringer Ingelheim, Lilly Japan, Chugai Pharma, Ono Pharmaceutical, Bristol Myers Squibb Japan, Shionogi, Daiichi Sankyo, Kyowa Hakko Kirin, Nippon Kayaku, Mundipharma, Novartis, PfizerConsulting or Advisory Role: AstraZeneca, Lilly Japan, MSDResearch Funding: Boehringer Ingelheim (Inst), Lilly Japan (Inst), Kyowa Hakko Kirin (Inst), Chugai Pharma (Inst), Shionogi (Inst)No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Updated PFS2 and OS. Kaplan-Meier curves for (A) corrected PFS2, (B) PFS2 with the same definition (events are true for the second PD in both groups), and (C) OS in patients treated with GCP and those treated with gefitinib-alone are shown. Plus symbols indicate censored patients at the data cutoff point. GCP, gefitinib and carboplatin plus pemetrexed; HR, hazard ratio; OS, overall survival; PD, progressive disease; PFS, progression-free survival.
FIG 2.
FIG 2.
Subgroup analysis of OS. Forest plots for OS are shown. A HR < 1 implies a lower risk of death with the GCP regimen than with gefitinib-alone. The Cox proportional hazards regression model includes randomly assigned treatments, subgroup covariates of interest, and treatment-by-subgroup interaction. ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; GCP, gefitinib and carboplatin plus pemetrexed; HR, hazard ratio; OS, overall survival.
FIG A1.
FIG A1.
Definition of (A) preplanned PFS2, (B) corrected PFS2, and (C) PFS2 with the same definition. CBDCA, carboplatin; GCP, gefitinib combined with carboplatin plus pemetrexed; PD, progressive disease; PEM, pemetrexed; PFS, progression-free survival.
FIG A2.
FIG A2.
CONSORT diagram. All patients except one ineligible patient and two who withdrew consent were randomly assigned to the gefitinib group or GCP group. One patient in the gefitinib group did not receive gefitinib-alone but was treated with the GCP regimen at the patient's request; thus, this patient's safety data were evaluated as if the patient was in the GCP group, whereas the PFS and OS data were evaluated as if the patient was in the gefitinib group on the basis of the intention to treat. One patient in the GCP group was excluded from the PFS analysis because the patient did not receive any protocol treatment; this patient was included in the OS analysis only. aOne patient received GCP instead of gefitinib monotherapy with a breach of allocation. GCP, gefitinib combined with carboplatin plus pemetrexed; OS, overall survival; PFS, progression-free survival.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hosomi Y, Morita S, Sugawara S, et al. : Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study. J Clin Oncol 38:115-123, 2020 - PubMed
    1. Royston P, Parmar MK: Restricted mean survival time: An alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome. BMC Med Res Methodol 13:152, 2013 - PMC - PubMed
    1. Uno H, Claggett B, Tian L, et al. : Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis. J Clin Oncol 32:2380-2385, 2014 - PMC - PubMed
    1. Sugawara S, Oizumi S, Minato K, et al. : Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902. Ann Oncol 26:888-894, 2015 - PubMed
    1. Noronha V, Patil VM, Joshi A, et al. : Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in EGFR-mutated lung cancer. J Clin Oncol 38:124-136, 2020 - PubMed

Publication types

MeSH terms