- Email: [email protected]
Randomized Phase III Study Comparing Gefitinib (G) with Erlotinib (E) in Patients (Pts) with Previously Treated Advanced Lung Adenocarcinoma (La): Wjog 5108L
Annals of Oncology 25 (Supplement 4): iv426–iv470, 2014 doi:10.1093/annonc/mdu349.50
NSCLC, metastatic RANDOMIZED PHASE III STUDY COMPARING GEFITINIB (G) WITH ERLOTINIB (E) IN PATIENTS (PTS) WITH PREVIOUSLY TREATED ADVANCED LUNG ADENOCARCINOMA (LA): WJOG 5108L
A. Nishiyama1, N. Katakami2, S. Morita3, T. Seto4, Y. Iwamoto5, T. Hirashima6, H. Kaneda7, T. Kawaguchi8, H. Matsuoka9, S. Yokota10, T. Nishimura11, M. Okada12, M. Fujita13, K. Shibata14, Y. Urata15, N. Yamamoto16, K. Nakagawa17, Y. Nakanishi18 1 Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, JAPAN 2 Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, JAPAN 3 Department of Biomedical Statistics and Bioinformatics, Kyoto University, Kyoto, JAPAN 4 Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, JAPAN 5 Medical Oncology, Hiroshima City Hospital, Hiroshima, JAPAN 6 Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, JAPAN 7 Department of Medical Oncology, Kinki University Faculty of Medicine, Osakasayama, JAPAN 8 Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, JAPAN 9 Department of Surgery, Hyogo Prefectural Awaji Medical Center, Sumoto, JAPAN 10 Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, JAPAN 11 Department of Respiratory Medicine, Kyoto Katsura Hospital, Kyoto, JAPAN 12 Surgical Oncology, Hiroshima University, Hiroshima, JAPAN 13 Department of Respiratory Medicine, Fukuoka University Hospital, Fukuoka, JAPAN 14 Department of Medical Oncology, Kouseiren Takaoka Hospital, Takaoka, JAPAN 15 Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, JAPAN 16 Third Department of Internal Medicine, Wakayama Medical University, Wakayama, JAPAN 17 Medical Oncology, Kinki University School of Medicine, Osakasayama, JAPAN 18 Research Institute for Diseases of The Chest, Kyushu University Hospital, Fukuoka, JAPAN
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from http://annonc.oxfordjournals.org/ by guest on November 30, 2015
abstracts
1271P
Aim: A multicenter randomized phase III study designed to demonstrate non-inferiority of G to E was conducted. Methods: 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], β =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). Results: 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]). Conclusions: 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. Disclosure: 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.
NSCLC, metastatic RANDOMIZED PHASE III STUDY COMPARING GEFITINIB (G) WITH ERLOTINIB (E) IN PATIENTS (PTS) WITH PREVIOUSLY TREATED ADVANCED LUNG ADENOCARCINOMA (LA): WJOG 5108L
A. Nishiyama1, N. Katakami2, S. Morita3, T. Seto4, Y. Iwamoto5, T. Hirashima6, H. Kaneda7, T. Kawaguchi8, H. Matsuoka9, S. Yokota10, T. Nishimura11, M. Okada12, M. Fujita13, K. Shibata14, Y. Urata15, N. Yamamoto16, K. Nakagawa17, Y. Nakanishi18 1 Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, JAPAN 2 Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, JAPAN 3 Department of Biomedical Statistics and Bioinformatics, Kyoto University, Kyoto, JAPAN 4 Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, JAPAN 5 Medical Oncology, Hiroshima City Hospital, Hiroshima, JAPAN 6 Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, JAPAN 7 Department of Medical Oncology, Kinki University Faculty of Medicine, Osakasayama, JAPAN 8 Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, JAPAN 9 Department of Surgery, Hyogo Prefectural Awaji Medical Center, Sumoto, JAPAN 10 Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, JAPAN 11 Department of Respiratory Medicine, Kyoto Katsura Hospital, Kyoto, JAPAN 12 Surgical Oncology, Hiroshima University, Hiroshima, JAPAN 13 Department of Respiratory Medicine, Fukuoka University Hospital, Fukuoka, JAPAN 14 Department of Medical Oncology, Kouseiren Takaoka Hospital, Takaoka, JAPAN 15 Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, JAPAN 16 Third Department of Internal Medicine, Wakayama Medical University, Wakayama, JAPAN 17 Medical Oncology, Kinki University School of Medicine, Osakasayama, JAPAN 18 Research Institute for Diseases of The Chest, Kyushu University Hospital, Fukuoka, JAPAN
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from http://annonc.oxfordjournals.org/ by guest on November 30, 2015
abstracts
1271P
Aim: A multicenter randomized phase III study designed to demonstrate non-inferiority of G to E was conducted. Methods: 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], β =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). Results: 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]). Conclusions: 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. Disclosure: 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.