1284P - Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Pathology/Molecular Biology
Personalised/Precision Medicine
Non-Small Cell Lung Cancer
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Osamu Ishimoto
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors O. Ishimoto1, S. Oizumi2, K. Minato3, T. Harada4, A. Inoue5, Y. Fujita6, M. Maemondo7, H. Yoshizawa8, K. Ito9, A. Gemma10, M. Nishitsuji11, M. Harada12, H. Isobe13, I. Kinoshita14, S. Morita15, K. Kobayashi16, K. Hagiwara17, M. Kurihara18, T. Nukiwa19
  • 1Respiratory Medicine, Sendai Kosei Hospital, 9800873 - Sendai/JP
  • 2First Department Of Medicine, Hokkaido University School of Medicine, 060-8638 - Sapporo/JP
  • 3Department Of Respiratory Medicine, Gunma Prefectural Cancer Center, 373-855 - Ohta/JP
  • 4Center For Respiratory Diseases, JCHO Hokkaido Hospital, 062-8618 - Sapporo/JP
  • 5Department Of Respiratory Medicine, Tohoku University, JP-980-8575 - Sendai/JP
  • 6Department Of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, Asahikawa/JP
  • 7Department Of Respiratory Medicine, Miyagi Cancer Center, Natori/JP
  • 8Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 951-8520 - Niigata/JP
  • 9Respiratory Medicine, Niigata City General Hospital, 9501197 - Niigata/JP
  • 10Pulmonary Medicine And Oncology, Nippon Medical School, Tokyo/JP
  • 11Respiratory Medicine, Ishikawa Prefectural Central Hospital, 9208530 - Kanazawa/JP
  • 12Department Of Pulmonary Disease, National Hospital Organization Hokkaido Cancer Center, 0030804 - Sapporo/JP
  • 13Clinical Oncology, KKR Sapporo Medical Center, 062-0931 - Sapporo/JP
  • 14Department Of Medical Oncology, Hokkaido University Graduate School of Medicine, 0608638 - Sapporo/JP
  • 15Department Of Biomedical Statistics And Bioinformatics, Kyoto University, Kyoto/JP
  • 16Respiratory Medicine, Saitama International Medical Center, 350-1298 - Saitama/JP
  • 17Department Of Respiratory Medicine, Saitama Medical University, Saitama/JP
  • 18The Chief Director, The Tokyo Cooperative Oncology Group, Tokyo/JP
  • 19Medical Commisioner, South Miyagi Medical Center, 9891253 - Miyagi/JP



The first-line combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) plus platinum-based doublet chemotherapy has yet to be sufficiently evaluated for patients with EGFR-mutant NSCLC. This randomized phase II study was designed to select the combination regimen for phase III evaluation.


Chemotherapy-naïve patients with advanced non-squamous EGFR-mutant NSCLC were randomly assigned to receive either a concurrent regimen (C group) or a sequential and alternating regimen (S group). Patients in the C group received concurrent G (250 mg daily) and CP (AUC = 6 and 500 mg/m2, day 1) of a 3-week cycle for 6 cycles, followed by concurrent G and P maintenance. Patients in the S group initially received G (days 1 to 28) and then CP (day 29 and 51); the cycle was repeated for 3 cycles, followed by alternating G and P maintenance. The primary endpoint was progression-free survival (PFS).


All 80 patients enrolled were eligible and evaluable for efficacy (41 in the C group and 39 in the S group). Median PFS was 18.3 months in the C group and 15.3 months in the S group (p = 0.20). Although overall survival data are immature (with a median follow-up time of 30.6 months, 16 and 24 death events), median survival times were 41.9 months in the C group, and were 30.7 months in the S group (p = 0.042). Response rates were similar in both groups (87.8% in the C group and 84.6% in the S group). Hematological and non-hematological adverse events were common and reversible; especially interstitial lung disease was not frequent (two cases in each group; 5% of all patients). In an exploratory analysis, there was no significant difference in post progression survival and overall survival between patients with progression of target or non-target lesions and those progressed with new lesions.


Both regimens had promising efficacy with predictable toxicities, although concurrent regimens may provide better overall survival. Considering the convenience in clinical practice, the concurrent regimen was chosen to compare with gefitinib monotherapy in ongoing phase III NEJ009 study.


S. Oizumi: Honoraria from AstraZeneca Reseach funding from Eli Lilly; A. Inoue: Reseach funding from Eli Lilly, AstraZeneca; M. Maemondo: Consultant or advisory role from AstraZeneca, Boeheringer Honoraria from AstraZeneca, Chugai, Boeheringer Reseach funding from Boeheringe; H. Yoshizawa: Honoraria from AstraZeneca, Chugai, Taiho, Ono,Behringer, Novartis, Phyzer,Daiichi-Sankyo,Hisamitsu, Eli Lilly Research funding from AstraZeneca, Chugai, Taiho, Ono,Behringer, Novartis, Phyzer,Daiichi-Sankyo,Hisamitsu, Eli Lilly; A. Gemma: Honoraria from AstraZeneca; S. Morita: Honoraria from Lilly, Astra Zeneca; K. Kobayashi: Honoraria from AstraZeneca; T. Nukiwa: Consultant or advisory role from Shionogi, Boehringer Honoraria from Shionogi, Kyowa, Novartis Other remuneration from Sekisui. All other authors have declared no conflicts of interest.