1271P - Randomized phase III study comparing gefitinib (G) with erlotinib (E) in patients (pts) with previously treated advanced lung adenocarcinoma (LA):...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cytotoxic agents
Non-small-cell lung cancer
Biological therapy
Presenter Akihiro Nishiyama
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors A. Nishiyama1, N. Katakami2, S. Morita3, T. Seto4, Y. Iwamoto5, T. Hirashima6, H. Kaneda7, T. Kawaguchi 8, H. Matsuoka9, S. Yokota10, T. Nishimura11, M. Okada12, M. Fujita13, K. Shibata14, Y. Urata15, N. Yamamoto16, K. Nakagawa17, Y. Nakanishi18
  • 1Department Of Respiratory Medicine, Kurashiki Central Hospital, 710-8602 - Kurashiki/JP
  • 2Division Of Integrated Oncology, Institute of Biomedical Research and Innovation, 650-0047 - Kobe/JP
  • 3Department Of Biomedical Statistics And Bioinformatics, Kyoto University, Kyoto/JP
  • 4Department Of Thoracic Oncology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 5Medical Oncology, Hiroshima city hospital, Hiroshima/JP
  • 6Department Of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic diseases, JP- 583-8588 - Osaka/JP
  • 7Department Of Medical Oncology, Kinki University Faculty of Medicine, Osakasayama/JP
  • 8Department Of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka/JP
  • 9Department Of Surgery, Hyogo Prefectural Awaji Medical Center, Sumoto/JP
  • 10Department Of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka/JP
  • 11Department Of Respiratory Medicine, Kyoto Katsura Hospital, Kyoto/JP
  • 12Surgical Oncology, Hiroshima University, 7348551 - Hiroshima/JP
  • 13Department Of Respiratory Medicine, Fukuoka University Hospital, Fukuoka/JP
  • 14Departmento Of Medical Oncology, Kouseiren Takaoka Hospital, JP-933-8555 - Takaoka/JP
  • 15Department Of Thoracic Oncology, Hyogo Cancer Center, 673-8558 - Akashi/JP
  • 16Third Department Of Internal Medicine, Wakayama Medical University, Wakayama/JP
  • 17Medical Oncology, Kinki University School of Medicine, JP-589-8511 - Osakasayama/JP
  • 18Research Institute For Diseases Of The Chest, Kyushu University Hospital, 812-8582 - Fukuoka/JP



A multicenter randomized phase III study designed to demonstrate non-inferiority of G to E was conducted.


Eligible pts were those with pathologically proven LA with stage IIIB/IV (AJCC version 6) or recurrence, previously treated with at least one chemotherapy regimen, evaluable disease, age ≥20 years and ECOG PS 0-2. Pts were randomized 1:1 to E (150 mg, daily), or G (250mg, daily) according to gender, stage, EGFR mutation status, performance status, smoking history, CT line, and institution. Target sample size was 560 based on the assumption that G was not inferior to E in PFS (2 – 4 months, α =0.025 [one sided], ß =0.80). Non-inferiority was to be concluded if the upper CI limit was < 1.30. The primary endpoint was PFS, and secondary endpoints included overall survival (OS), response rate (RR), disease control rate (DCR), safety, and time to treatment failure (TTF).


From 2009/7 to 2012/10, 561 pts were accrued, and 280 and 279 were randomly assigned to E and G, respectively, including 185 (66.1%, E) and 186 (66.7%, G) with EGFR mutated tumors. Other baseline factors were balanced between arms except PS: median age 67/68 years; % female 54/55; % PS = 0, 50/40; PS = 1, 43/54; % stage IV, 69/69; % 2nd line, 69/71, % smoker, 50/50; for E/G. Median PFS, TTF and OS for E/G were 7.5 m/6.5 m (p = 0.257, HR = 1.125, 95% CI: 0.940-1.347), 5.3 m/5.6 m (HR = 1.032, 95% CI: 0.866-1.231), and 24.5 m/22.8 m (HR = 1.038, 95% CI: 0.833-1.294), respectively. RR and DCR for E/G were 43.9%/46.1% and 75.0%/71.2%, respectively. Median PFS and OS in pts with EGFR mutation for E/G were 10.1 m/8.9 m (p = 0.532), and 32.0 m/26.6 m (p = 0.111), respectively. Exploratory subset analysis revealed the prolongation of PFS of E compared with that of G in pts aged <65 (p = 0.032, HR = 1.357, 95% CI: 1.024-1.799). Main grade 3/4 toxicities were rash (18.1% [E] v 2.2% [G]) and elevation of AST/ALT (2.2%/3.3% [E] v 6.1%/13.0% [G]).


Non-inferiority in PFS between E and G was not demonstrated according to predefined criteria; however, there was no statistically significant difference in PFS, OS, RR, DCR and TTF.


S. Morita: other substantive relationships: Chugai, AstraZeneka; T. Seto: corporate-sponsored research: AstraZeneka other substantive relationships: AstraZeneka, Chugai; T. Hirashima: corporate-sponsored research: Astrazeneca, Chugai-pharm; M. Okada: corporate-sponsored research: AstraZeneka, Chugai, Roche other substantive relationships: AstraZeneka, Chugai, Roche; Y. Urata: other substantive relationships: Chugai, AstraZeneka; N. Yamamoto: other substantive relationships: AstraZeneka, Chugai; K. Nakagawa: corporate-sponsored research: AstraZeneka, Chugai other substantive relationships: AstraZeneka, Chugai; Y. Nakanishi: corporate-sponsored research: Chugai other substantive relationships: Chugai. All other authors have declared no conflicts of interest.