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Randomised Study of Axitinib (Axi) Plus Best Supportive Care (Bsc) Versus Placebo (Pbo) Plus Bsc in Patients with Advanced Hepatocellular Carcinoma (Hcc) Following Prior Antiangiogenic Therapy
Annals of Oncology 25 (Supplement 5): v1–v41, 2014 doi:10.1093/annonc/mdu438.17
LBA17
abstracts
Y-K. Kang1*, T. Yau2*, J-W. Park3, E. Boucher4, H.Y. Lim5, R.T.P. Poon6, T-Y. Lee7, S. Obi8, S.L. Chan9, SK. Qin10, R.D. Kim11, J. Tang12, O. Valota13, D. Chakrabarti14, M. Kudo15 1 Oncology, Asan Medical Center, University of Ulsan, Seoul, KOREA 2 Medicine, Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, CHINA 3 Center for Liver Cancer, National Cancer Center, Goyang, KOREA 4 Medical Oncology, Centre Eugène Marquis, Rennes, FRANCE 5 Hematology-oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, KOREA 6 Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, CHINA 7 Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung City, TAIWAN 8 Hepatology, Sasaki Foundation Kyoundo Hospital, Tokyo, JAPAN 9 Clinical Oncology, Prince of Wales Hospital, Hong Kong, CHINA 10 PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, CHINA 11 Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA 12 Oncology Business Unit, Pfizer Inc, New York, NY, USA 13 Clinical Oncology, Pfizer Italia SRL, Milan, ITALY 14 Oncology, Pfizer Inc, Collegeville, PA, USA 15 Gastroenterology and Hepatology, Kinki University Hospital, Osaka, JAPAN * Equal contribution
Aim: The efficacy and safety of Axi, a potent and selective inhibitor of VEGF receptors 1-3, was evaluated in a global, randomised, double-blind phase II clinical trial in patients ( pts) with locally advanced or metastatic HCC. Methods: Eligible pts progressed on or were intolerant to 1 prior antiangiogenic therapy and had ECOG performance status 0 or 1. Pts were randomised 2:1 to receive Axi + BSC or Pbo + BSC at a starting dose of 5 mg twice daily and stratified by tumour invasion ( presence vs absence of extrahepatic spread and/or vascular invasion) and geographic region (Asia vs non-Asia). Primary end point was OS and secondary end points included ORR, PFS and safety. The study had 80% power to detect an improvement in median OS (mOS) from 5.0 to 8.3 mo with Axi + BSC, corresponding to a HR 0.60 (1-sided α = 0.025). Results: Two hundred two pts (134 Axi vs 68 Pbo), predominantly of Asian origin (63 vs 62%), were randomised. Baseline pt characteristics and stratification factors were well balanced between the Axi vs Pbo arms. All pts were in Child-Pugh A category and 76% of pts in both arms had tumour invasion. mOS with Axi was 12.7 mo (95% CI: 10.2, 14.9) vs 9.7 mo (95% CI: 5.9, 11.8) with Pbo and was not statistically significant (HR 0.870; 95% CI: 0.620, 1.222; 1-sided stratified P = 0.211). Investigator-assessed median PFS (mPFS) with Axi was 3.6 mo vs 1.9 mo with Pbo and was statistically significant (HR 0.618; 95% CI: 0.438, 0.871; P = 0.004). ORR was 9.7% with Axi vs 2.9% with Pbo (P = 0.083). More pts discontinued due to AE with Axi vs Pbo (23 vs 13%). Most common all causality AEs (Axi vs Pbo, % of pts) were diarrhoea (54 vs 12%), hypertension (54 vs 13%), decreased appetite (47 vs 21%), fatigue (35 vs 26%), abdominal pain (34 vs 21%), hand-foot syndrome (34 vs 6%), weight decrease (27 vs 3%), nausea (26 vs 10%), dysphonia and hypothyroidism (25 vs 0% each). Conclusions: Axi + BSC did not demonstrate statistically significant improvement in mOS but improved mPFS compared to Pbo + BSC in pts with advanced HCC who received prior antiangiogenic therapy. Safety profile with Axi was consistent with earlier clinical trials and no new safety signal was detected. Disclosure: Y. Kang: I have been a consultant for Pfizer Inc and Bayer Healthcare Pharmaceuticals; J. Park: I am (was) a member of Consultancy/Advisory Board of Taiho Pharmaceutical, Bayer Healthcare Pharmaceuticals, and Roche, and received honorarium from Taiho Pharmaceutical and research funding from Bayer Healthcare
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/mdu438.17/1746465 by guest on 26 October 2019
RANDOMISED STUDY OF AXITINIB (AXI) PLUS BEST SUPPORTIVE CARE (BSC) VERSUS PLACEBO (PBO) PLUS BSC IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA (HCC) FOLLOWING PRIOR ANTIANGIOGENIC THERAPY
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
LBA17
abstracts
Y-K. Kang1*, T. Yau2*, J-W. Park3, E. Boucher4, H.Y. Lim5, R.T.P. Poon6, T-Y. Lee7, S. Obi8, S.L. Chan9, SK. Qin10, R.D. Kim11, J. Tang12, O. Valota13, D. Chakrabarti14, M. Kudo15 1 Oncology, Asan Medical Center, University of Ulsan, Seoul, KOREA 2 Medicine, Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, CHINA 3 Center for Liver Cancer, National Cancer Center, Goyang, KOREA 4 Medical Oncology, Centre Eugène Marquis, Rennes, FRANCE 5 Hematology-oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, KOREA 6 Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, CHINA 7 Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung City, TAIWAN 8 Hepatology, Sasaki Foundation Kyoundo Hospital, Tokyo, JAPAN 9 Clinical Oncology, Prince of Wales Hospital, Hong Kong, CHINA 10 PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, CHINA 11 Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA 12 Oncology Business Unit, Pfizer Inc, New York, NY, USA 13 Clinical Oncology, Pfizer Italia SRL, Milan, ITALY 14 Oncology, Pfizer Inc, Collegeville, PA, USA 15 Gastroenterology and Hepatology, Kinki University Hospital, Osaka, JAPAN * Equal contribution
Aim: The efficacy and safety of Axi, a potent and selective inhibitor of VEGF receptors 1-3, was evaluated in a global, randomised, double-blind phase II clinical trial in patients ( pts) with locally advanced or metastatic HCC. Methods: Eligible pts progressed on or were intolerant to 1 prior antiangiogenic therapy and had ECOG performance status 0 or 1. Pts were randomised 2:1 to receive Axi + BSC or Pbo + BSC at a starting dose of 5 mg twice daily and stratified by tumour invasion ( presence vs absence of extrahepatic spread and/or vascular invasion) and geographic region (Asia vs non-Asia). Primary end point was OS and secondary end points included ORR, PFS and safety. The study had 80% power to detect an improvement in median OS (mOS) from 5.0 to 8.3 mo with Axi + BSC, corresponding to a HR 0.60 (1-sided α = 0.025). Results: Two hundred two pts (134 Axi vs 68 Pbo), predominantly of Asian origin (63 vs 62%), were randomised. Baseline pt characteristics and stratification factors were well balanced between the Axi vs Pbo arms. All pts were in Child-Pugh A category and 76% of pts in both arms had tumour invasion. mOS with Axi was 12.7 mo (95% CI: 10.2, 14.9) vs 9.7 mo (95% CI: 5.9, 11.8) with Pbo and was not statistically significant (HR 0.870; 95% CI: 0.620, 1.222; 1-sided stratified P = 0.211). Investigator-assessed median PFS (mPFS) with Axi was 3.6 mo vs 1.9 mo with Pbo and was statistically significant (HR 0.618; 95% CI: 0.438, 0.871; P = 0.004). ORR was 9.7% with Axi vs 2.9% with Pbo (P = 0.083). More pts discontinued due to AE with Axi vs Pbo (23 vs 13%). Most common all causality AEs (Axi vs Pbo, % of pts) were diarrhoea (54 vs 12%), hypertension (54 vs 13%), decreased appetite (47 vs 21%), fatigue (35 vs 26%), abdominal pain (34 vs 21%), hand-foot syndrome (34 vs 6%), weight decrease (27 vs 3%), nausea (26 vs 10%), dysphonia and hypothyroidism (25 vs 0% each). Conclusions: Axi + BSC did not demonstrate statistically significant improvement in mOS but improved mPFS compared to Pbo + BSC in pts with advanced HCC who received prior antiangiogenic therapy. Safety profile with Axi was consistent with earlier clinical trials and no new safety signal was detected. Disclosure: Y. Kang: I have been a consultant for Pfizer Inc and Bayer Healthcare Pharmaceuticals; J. Park: I am (was) a member of Consultancy/Advisory Board of Taiho Pharmaceutical, Bayer Healthcare Pharmaceuticals, and Roche, and received honorarium from Taiho Pharmaceutical and research funding from Bayer Healthcare
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/mdu438.17/1746465 by guest on 26 October 2019
RANDOMISED STUDY OF AXITINIB (AXI) PLUS BEST SUPPORTIVE CARE (BSC) VERSUS PLACEBO (PBO) PLUS BSC IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA (HCC) FOLLOWING PRIOR ANTIANGIOGENIC THERAPY
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].