499O - Phase II study of first-line mFOLFOX plus cetuximab (C) for 8 cycles followed by mFOLFOX plus C or single agent (s/a) C as maintenance therapy in p...

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
Presenter Pilar García Alfonso
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors P. García Alfonso1, M. Benavides2, A. Sánchez Ruiz3, C. Guillen-Ponce4, M.J. Safont5, J. Alcaide6, A. Gómez7, R. Lopez8, J.L. Manzano9, M. Mendez Urena10, F. Rivera11, J. Sastre12, C. Grávalos13, T. García García14, J.I. Martin-Valades15, E. Falco16, E. González Flores17, M. Navalón18, E. Diaz Rubio19, E. Aranda20
  • 1Medical Oncology, Gregorio Marañon Hospital, 28007 - Madrid/ES
  • 2Medical Oncology, Hospital Regional Universitario Carlos Haya, Málaga/ES
  • 3Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid/ES
  • 4Medical Oncology, Hospital General Universitario Ramón y Cajal, Madrid/ES
  • 5Medical Oncology, Hospital General de Valencia, Valencia/ES
  • 6Department Of Medical Oncology, Hospital COSTA DEL SOL, 29600 - MARBELLA/ES
  • 7Medical Oncology, Hospital Reina Sofía, Córdoba/ES
  • 8Medical Oncology, Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, 15706 - Santiago de Compostela/ES
  • 9Medical Oncology, ICO Hospital Germans Trias i Pujol, Barcelona/ES
  • 10Medical Oncology, Hospital General de Mostoles, ES-28935 - Mostoles/ES
  • 11Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander/ES
  • 12Medical Oncology, Hospital Universitario Clínico San Carlos, 28040 - Madrid/ES
  • 13Medical Oncology, Hospital Universitario Doce de Octubre, Madrid/ES
  • 14Medical Oncology, Hospital Morales Meseguer, Murcia/ES
  • 15Oncology, Fundación Jiménez Díaz, Madrid/ES
  • 16Medical Oncology, Hospital Son Llatzer, Palma de Mallorca/ES
  • 17Medical Oncology, Hospital Virgen de las Nieves, Granada/ES
  • 18Medical Oncology, Complejo Asistencial de Zamora, Zamora/ES
  • 19Oncologia Medica, Hospital Clinico Universitario San Carlos, ES-28040 - Madrid/ES
  • 20Oncology Department, IMIBIC-Hospital Reina Sofía, Córdoba/ES



The optimal duration and content of first-line therapy in p with mCRC once they have achieved the maximal response remains controversial. This multicenter, randomized, phase II study was aimed to evaluate the efficacy and tolerability of 8 cycles of mFOLFOX plus C followed by maintenance mFOLFOX plus C or s/a C.


Previously untreated wild-type KRAS exon 2 mCRC p were randomized to receive C (250 mg/m2) weekly + mFOLFOX-6 q2w x 8 cycles continued by maintenance therapy with s/a C (Arm A) or mFOLFOX-6 plus C (Arm B) until progression. The primary endpoint was progression-free survival (PFS); secondary endpoints: overall survival (OS), objective response rate (ORR) and safety. The statistical design was based on a non-inferiority hypothesis in % of p free of progression at 9 months (m); 47% in arm B and maximum difference of 15% in arm A; sample size of 192 pts (sample ratio 2:1/A:B), significance level 0.1 and power of 80%.


193 p (median age 60 years, range 33–74) were randomized: 129 Arm A, 64 Arm B; no significant differences in demographic characteristics. Median follow-up was 14 months (range: 0–38). There were not statistically significant differences in ORR, PFS and OS between the 2 arms. Preliminary analysis of safety shows that tolerability was acceptable in the 2 arms, with grade 3/4 neutropenia in 25% and 26%, rash acneiform in 13% and 23%, neuropathy in 2% and 15% (p < 0.001), asthenia 8% and 5%, diarrhea in 7% and 6%, mucositis in 7% and 6% in Arms A and B, respectively. Analysis of efficacy according to tumor RAS mutations is ongoing.


C as a maintenance therapy following induction mFOLFOX plus C was not inferior to continuation mFOLFOX plus C. This study suggests that maintenance therapy with s/a C is an appropriate option following induction mFOLFOX in pts with mCRC.

Efficacy Arm A Arm B p-value HR/OR [95% CI]
mPFS, months 8.9 9.8 0.09 HR: 0.690 (0.4498, 1.0580)
mOS, months 23.6 22.2 0.54 HR: 1.151 (0.7330, 1.8070)
ORR, % 47 39 0.33 OR: 1.3565 (0.7372, 2.4961)
PFS 9m rate, % 64 72 0.25 OR: 0.6827 (0.3556, 1.3108)


M. Benavides: Honoraria: Merck, Roche and Amgen; F. Rivera: Consultant or advisory role: Merck, Amgen, Roche Honoraria: Merck, Amgen, Roche Research funding: Merck, Amgen, Roche; E. Diaz Rubio: Consultant or Advisory Role: Merck Honoraria: Merck Research Funding: Merck; E. Aranda: Consultant or advisory Role: Roche, Merck. All other authors have declared no conflicts of interest.