476P - Phase II clinical trial with axitinib as maintenance therapy in patients (p) with metastatic colorectal carcinoma (CRC)

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Colon and Rectal Cancer
Presenter Cristina Gravalos
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors C. Gravalos1, A. Carrato2, M. Tobeña3, E. Grande Pulido2, G. Soler4, J. Vieitez5, L. Robles6, M. Valladares-Ayerbes7, E. Polo8, M.L. Limon9, M.J. Safont10, C. Lopez11, P. García Alfonso12, E. Aranda13
  • 1Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 2Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 3Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 - Barcelona/ES
  • 4Medical Oncology, ICO Hospital Duran i Reynals, Hospitalet/ES
  • 5Medical Oncologist, Hospital Universitario Central de Asturias, Oviedo/ES
  • 6Medical Oncology, University Hospital 12 De Octubre, 28031 - Madrid/ES
  • 7Medical Oncology, Hospital Universitario a Coruna - a Corunac, A Coruna/ES
  • 8Medical Oncology, Hospital Miguel Servet, Zaragoza/ES
  • 9Medical Oncology, Hospital Universitario Virgen del Rocio, Sevilla/ES
  • 10Medical Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 11Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander/ES
  • 12Medical Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 13Medical Oncology, Reina Sofía Hospital, University of Córdoba, Maimonides Institute of Biomedical Research (IMIBIC). Spanish Cancer Network (RTICC), Instituto de Salud Carlos III,, 14004 - Cordoba/ES



The prognosis of advanced CRC p has improved during last years. Nevertheless, treatment options in this situation are still limited. Maintenance therapy with bevacizumab has been stablished as standard of care after bevacizumab plus fluropyrimidine based chemotherapy. Axitinib is a novel drug targeting VEGFR1, 2 and 3, with contradictory results in CRC


In this phase 2 randomized double blinded trial, axitinib (5 mg/bid) was compared to placebo in metastatic CRC p who had not progressed after 6-8 months of first line treatment with chemotherapy with or without bevacizumab or cetuximab. The primary objective was progression-free survival (PFS) at 6 months. Secondary objectives included overall survival (OS), response rate (RR) and safety


A total of 49 p were included: 25 cohort A (axitinib) and 24 cohort B (placebo). Baseline characteristics were well balanced. Mean age was 66 years (Standard Deviation (SD) ±10.35); 33 (67%) were men; ECOG Performance status was 0 for 19 p and 1 for 30 p. PFS at 6 months was 40% (Confidence Interval (CI) 95% 21.28, 58.12) for cohort A and 8.33% (CI95% 1.44, 23.30) for cohort B; p-value p = 0.01. Median PFS was 4.96 months in cohort A and 3.16 months for cohort B; Hazard Ratio (HR) 0.46 (0.2515, 0.8565), p = 0.0116. Median OS was 27.61 months in cohort A (CI: 14.96; 38.94), and 19.99 months (CI: 12.08; 27.35) in cohort B, p = 0.3279. The study was prematurely closed due to lack of accrual; however p-value of the log-rank contrast was significant. Regarding safety, grade 3-4 treatment related toxicities were experienced by 7 p (28%) in cohort A and 1 p (4%) in cohort B. The most frequent grade 3-4 treatment related toxicities were hypertension in 6% and 2%; diarrhea in 4% and 0%, asthenia in 2% and 0% in cohort A and B, respectively. There were no toxic deaths


Maintenance treatment with axitinib in advanced CRC with no progression after first line chemotherapy is associated with a significantly increased PFS when compared to placebo. Axitinib was well tolerated with few SAEs. The initially estimated sample size was not reached, but the study drug should be further studied in this setting since promising efficacy data were met

Clinical trial identification

EudraCT: 2011-002384-16

Legal entity responsible for the study

Spanish Cooperative Group for the Digestive Tumour Therapy


Pfizer, New York, NY, USA


A. Carrato: Consultant or advisore role: Amgen, Merck, Roche. M. Valladares-Ayerbes: Consultant or advisory role: Amgen, Bayer. C. Lopez: Consultant or advisory role Amgen, Pfizer, Celgene, Sanofi, Roche, Novartis, Ipsen. P. García Alfonso: Advisory role: Roche, Merck, Amgen, Sanofi, Lilly y Bayer. E. Aranda: advisory role from Amgen, Bayer, Celgene, Merk, Roche and Sanofi. All other authors have declared no conflicts of interest.