PD-005 - Combined analysis of two randomised Phase II trials comparing the efficacy and safety of nintedanib versus sorafenib in Caucasian and Asian patients...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anticancer agents
Hepatobiliary Cancers
Biological Therapy
Presenter D. Palmer
Citation Annals of Oncology (2015) 26 (suppl_4): 101-107. 10.1093/annonc/mdv234
Authors D. Palmer1, P. Ross2, T. Meyer3, Y. Chao4, A. Deptala5, L. Fartoux6, Y.-. Feng7, J. Graham8, D.-. Lin9, Y.T. Ma10, M. Peck-Radosavljevic11, B.-. Ryoo12, C.-. Yen13, J. Hocke14, S. Vlassak15, A. Wenz16, A.-. Loembe17, A.-. Cheng18
  • 1Translational Medicine University of Liverpool, Liverpool/UK
  • 2King's College Hospital NHS Foundation Trust, London/UK
  • 3UCL Cancer Institute, London/UK
  • 4Taipei Veterens General Hospital, Taipei City/TW
  • 5Central Clinical Hospital of the Ministry of Interior, Warsaw/PL
  • 6Hopital Saint Antoine, Paris/FR
  • 7Chi Mei Medical Center, Tainan City/TW
  • 8Beatson West of Scotland Cancer Centre, Glasgow/UK
  • 9Chang Gung Memorial Hospital & Chang Gung University, Guishan/TW
  • 10University of Birmingham, Birmingham/UK
  • 11Medizinische Universität Wien, Vienna/AT
  • 12Asan Medical Center, Seoul/KR
  • 13National Cheng Kung University Hospital, Tainan/TW
  • 14Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß/DE
  • 15SCS Boehringer Ingelheim Comm. V, Brussels/BE
  • 16Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/DE
  • 17Boehringer Ingelheim B.V., Alkmaar/NL
  • 18National Taiwan University Hospital, Taipei City/TW



Nintedanib is an oral, triple angiokinase inhibitor of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors. Nintedanib in combination with docetaxel is approved in the European Union for the treatment of patients with locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma histology after first-line chemotherapy. Two randomised, multicentre, open-label, Phase II studies evaluated the efficacy and safety of nintedanib versus sorafenib in Caucasian patients (NCT01004003; 1199.37) and Asian patients (NCT00987935; 1199.39) with advanced hepatocellular carcinoma (HCC).


Enrolled patients had unresectable, advanced HCC, ECOG-PS ≤2, Child–Pugh score A, alanine/aspartate aminotransferase (ALT/AST) ≤2 × upper limit of normal and ≥1 untreated measurable lesion or lesion previously treated by loco-regional therapy with progression (by RECIST 1.0). Patients were randomised 2:1 to nintedanib 200 mg bid or sorafenib 400 mg bid continuously in 28-day cycles, until intolerable adverse events (AEs) or disease progression (PD); treatment beyond PD was allowed if clinical benefit was perceived. The primary endpoint was time to progression (TTP) by independent central review (ICR; RECIST 1.0); secondary endpoints included overall survival (OS) and objective tumour response (OR) by ICR. Safety was evaluated by the incidence and intensity of AEs (CTCAE 3.0).


Across two trials, 188 patients received nintedanib (Caucasian: n = 62; Asian: n = 63) or sorafenib (Caucasian: n = 31; Asian: n = 32). Main patient demographics/baseline characteristics were balanced between treatments in both trials except for macrovascular invasion (nintedanib vs sorafenib; 48% vs 31%) and a-fetoprotein (AFP) levels (AFP >20 mg/L; 76% vs 66%) in the Asian study. Thirty Caucasian patients and 21 Asian patients were treated beyond PD. TTP was comparable between nintedanib and sorafenib (median 3.7 vs 3.9 months; HR 1.31 [95% CI: 0.89–1.91]), as were OS (median 11.4 vs 11.0 months; HR 0.91 [95% CI: 0.65–1.29]) and OR rate (4% vs 5%). The rate of patients with Grade ≥3 AEs (62% vs 87%) and AEs leading to dose reduction (19% vs 51%) was lower with nintedanib than with sorafenib; more nintedanib-treated patients had AEs leading to drug discontinuation (34% vs 29%). The most frequent (>5% of patients in any group; nintedanib vs sorafenib) Grade ≥3 AEs were diarrhoea (10% vs 5%), fatigue (7% vs 2%), increased AST (8% vs 13%) and ALT (6% vs 8%), anaemia (7% vs 6%), malignant neoplasm progression (6% vs 8%), thrombocytopenia (5% vs 8%), skin reaction (1% vs 6%) and palmar–plantar erythrodysesthesia syndrome (0 vs 19%).


Combined analysis of two trials in Caucasian and Asian patients showed similar efficacy between nintedanib and sorafenib. AEs were as expected based on the safety profile of both agents; nintedanib-treated patients reported fewer Grade ≥3 AEs and AEs leading to dose reduction. Further studies of nintedanib in patients with advanced HCC are warranted.