P-272 - Phase II study of Regorafenib as single agent for the treatment of patients with metastatic colorectal cancer with any RAS or BRAF mutation and prev...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anticancer agents
Colon and Rectal Cancer
Biological Therapy
Presenter P. García Alfonso
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors P. García Alfonso1, C. Guillen-Ponce2, M.J. Ortiz1, G. Durán3, E. Falcó4, A. Muñoz5, B. García-Paredes6, M. Salgado7, A. López-Ladrón8, J.M. Vieitez de Prado9, M. Valladares10, A. Salud11, R. Lopez12, L. Robles13, A. Juárez14, S. Serrano15, C. Montagut16, M. Zanui17, M. Gil Raga18, A. La Casta19, M. Benavides20, E. Aranda1
  • 1Hospital General Universitario Gregorio Marañón, Madrid/ES
  • 2IRYCIS, Madrid/ES
  • 3H. Universitario Regional y Virgen de la Victoria, Málaga/ES
  • 4Hospital Son Llatzer, Palma de Mallorca/ES
  • 5H Gregorio Marañón, Madrid/ES
  • 6Hospital Clínico San Carlos, Madrid/ES
  • 7Complejo Hospitalario Universitario de Ourense, Orense/ES
  • 8H Nuestra Señora de Valme, Sevilla/ES
  • 9Asturias Central University Hospital, Oviedo/ES
  • 10Complejo Hospitalario Universitario La Coruña, La Coruña/ES
  • 11H Lleida Arnau de Vilanova, Lérida/ES
  • 12Santiago de Compostela, Santiago de Compostela/ES
  • 13Hospital 12 de Octubre, Madrid/ES
  • 14Hospital General de Elda, Elda/ES
  • 15Hospital San Joan de Reus, Reus/ES
  • 16Hospital Universitari del Mar, Barcelona/ES
  • 17Hospital de Mataró, Mataró/ES
  • 18Hospital de Sagunto, Puerto de Sagunto/ES
  • 19Hospital de Donostia, San Sebastián/ES
  • 20Hospital Regional Universitario Carlos Haya, Málaga/ES



Concomitant treatment with 5-FU, oxaliplatin and irinotecan in combination with bevacizumab (FOLFOXIRI-BEV) has demonstrated high activity and manageable toxicity and is considered as a valuable first-line option, especially for patients (pts) with RAS and/or BRAF mutated metastatic colorectal cancer (mCRC). The up-front use of this regimen raises questions about possible options for subsequent therapies. Regorafenib (REG) is an oral multikinase inhibitor that has shown benefit in overall and progression free survival (PFS) over placebo in pts with pretreated mCRC. This trial will assess safety and tolerability of regorafenib as a single agent in pts with RAS or BRAF mutant mCRC previously treated with FOLFOXIRI-BEV.


This is a multicenter phase II, single-arm, open-label study (NCT02175654). Main inclusion criteria are mCRC with any RAS or BRAF mutation; prior treatment with FOLFOXIRI-BEV regimen and progression ≤ 6 months of last dose, PS ≤ 1; evaluable disease by the RECIST criteria v1.1; adequate bone marrow, renal and hepatic function; life expectancy ≥ 90 days. Main exclusion criteria are clinically significant cardiac disease or myocardial infarction within the last 6 months, prior or concurrent presence of another neoplastic disease, and central nervous system metastases. Pts will receive regorafenib 160 mg PO, 3 weeks on/1 week off in a 4-week cycle. The primary endpoint is PFS rate at 6 months. 53 pts are needed to demonstrate that the treatment is effective if PFS rate at 6 months is higher than 30% and to reject the null hypothesis (PFS rate at 6 months ≤ 15%), considering an alpha error of 0.05 and a power of 80%.

Up to date, 7 (13%) pts have been included in the study.

The best treatment option for pts with RAS or BRAF mutated mCRC who have failed prior FOLFOXIRI-BEV remains an open question in the daily clinical practice. Regorafenib is an active and promising agent that could fill up this gap.