LBA17 - Randomised study of axitinib (Axi) plus best supportive care (BSC) versus placebo (Pbo) plus BSC in patients with advanced hepatocellular carcinoma...

Date 28 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, non-colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
Hepatobiliary Cancers
Presenter Yoon-Koo Kang
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors Y. Kang1, T. Yau2, J. Park3, E. Boucher4, H.Y. Lim5, R.T.P. Poon6, T. Lee7, S. Obi8, S.L. Chan9, S.K. Qin10, R.D. Kim11, J. Tang12, O. Valota13, D. Chakrabarti14, M. Kudo15
  • 1Oncology, Asan Medical Center, University of Ulsan, 138-736 - Seoul/KR
  • 2Medicine, The University of Hong Kong, Hong Kong/HK
  • 3Center For Liver Cancer, National Cancer Center, Goyang/KR
  • 4Medical Oncology, Centre Eugène Marquis, Rennes cedex/FR
  • 5Hematology-oncology, Samsung Medical Center, Sungkyunkwan University, Seoul/KR
  • 6Surgery, Queen Mary Hospital, The University of Hong Kong, - - Hong Kong/HK
  • 7Gastroenterology And Hepatology, Taichung Veterans Gene, Taichung City/TW
  • 8Hepatology, Sasaki Foundation Kyoundo Hospital, Tokyo/JP
  • 9Clinical Oncology, Prince of Wales Hospital, Hong Kong/HK
  • 10Pla Cancer Center, Nanjing Bayi Hospital, 210002 - Nanjing/CN
  • 11Oncology, H. Lee Moffitt Cancer Center, Tampa/US
  • 12Oncology Business Unit, Pfizer Inc, New York/US
  • 13Clinical Oncology, PFIZER ITALIA SRL, Milan/IT
  • 14Oncology, Pfizer Inc, Collegeville/US
  • 15Gastroenterology And Hepatology, Kinki University Hospital, 589-8511 - Osaka/JP

Abstract

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 Pharmaceuticals; S.L. Chan: I received research funding from Pfizer Inc.; J. Tang and O. Valota: I am employed by and own stock in Pfizer; D. Chakrabarti: is an employee of and owns stock in Pfizer.All other authors have declared no conflicts of interest.