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 Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
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.