LBA-05 - Results from the large, open-label phase 3b CONSIGN study of regorafenib in patients with previously treated metastatic colorectal cancer

Date 04 July 2015
Event WorldGI 2015
Session Oral and LBA abstracts
Topics Anticancer agents
Colon and Rectal Cancer
Biological Therapy
Presenter Eric Van Cutsem
Citation Annals of Oncology (2015) 26 (suppl_4): 117-122. 10.1093/annonc/mdv262
Authors E. Van Cutsem1, F. Ciardiello2, A. Grothey1, A. Falcone3, A. Zaniboni4, J. Kalmus5, R. Garcia-Carbonero6, J. Seitz7, R. Hofheinz8, U. Verma9, A. Miriyala1, J. Shapiro10
  • 1University Hospitals Leuven, Leuven/BE
  • 2Seconda Universita Degli Studi Di Napoli, Naples/IT
  • 3University of Pisa, Pisa/IT
  • 4Casa di Cura Poliambulanza, Brescia/IT
  • 5Bayer Pharma AG, Berlin/DE
  • 6Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBIS), Sevilla/ES
  • 7Aix-Marseille University, Marseille/FR
  • 8Universitaetsmedizin Mannheim, Mannheim/DE
  • 9Dallas/US
  • 10Whippany/US



Regorafenib is an oral multikinase inhibitor that targets tumor angiogenesis, oncogenesis, and the tumor microenvironment. The CORRECT phase 3 trial showed that regorafenib significantly improves survival compared with placebo in patients with previously treated metastatic colorectal cancer (mCRC) and led to regulatory approval in this setting. CONSIGN (NCT01538680) was initiated to allow patients with mCRC access to regorafenib before marketing authorization and to characterize the safety of regorafenib in a large cohort of patients (primary objective).


CONSIGN was a prospective, open-label, single-arm study carried out at 188 sites in 25 countries. Patients with mCRC who progressed after approved standard therapies and had ECOG performance status (PS) 0─1 received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle. Treatment was continued until disease progression, death, or unacceptable toxicity; treatment beyond progression was at the investigator's discretion. The primary endpoint was safety. Progression-free survival (PFS) (per investigator assessment) was the only efficacy variable assessed.


A total of 2872 patients were assigned to treatment from April 2012 to December 2013. The cut-off date for this analysis was January 2, 2015. The safety analysis includes 2864 patients who received treatment. Patients were a median 62 years of age, 53% had an ECOG PS of 1, and 47% had an ECOG PS of 0. Fifty-one percent of patients had a KRAS mutation; 96% had received ≥2 prior regimens for metastatic disease. The median duration of treatment was 2.5 months (range 0─30). NCI-CTCAE v4.0 grade ≥3 adverse events (AEs) occurred in 80% of patients (Table). Grade 5 treatment-emergent AEs occurred in 16% of patients, but were deemed drug-related in 0.5%. Grade ≥3 treatment-emergent hepatobiliary disorders occurred in 4% of patients. Treatment-emergent laboratory toxicities with grades ≥3 included increased bilirubin (13%), increased aspartate aminotransferase (AST; 7%), increased alanine aminotransferase (ALT; 6%), anemia (4%), thrombocytopenia (2%), and neutropenia (1%). One non-fatal case of severe drug-induced liver injury according to International DILI Working Group criteria (Aithal et al. 2011) was identified. Estimated median PFS was 2.7 (95% CI: 2.6–2.7) months (2.8 months KRAS wild-type, 2.5 months KRAS mutant).


In this large, prospective study in patients with previously treated mCRC, the safety profile of regorafenib was consistent with data from phase 3 trials in mCRC. PFS was in the range of that reported with regorafenib in this setting and similar across KRAS wild-type and mutant subgroups.