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Eur J Cancer. 2017 Aug;81:191-202. doi: 10.1016/j.ejca.2017.04.024. Epub 2017 Jun 19.

First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD).

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Ramon y Cajal University Hospital, Ramon y Cajal Institute for Health Research - IRYCIS, Alcala University, CIBERONC, Carretera de Colmenar Viejo, km 9.100, ES-28034 Madrid, Spain. Electronic address:
Germans Trias i Pujol Hospital-ICO, Carretera de Canyet s/n, ES-08916 Badalona, Spain.
Alicante General Hospital, Pintor Baeza, 11, ES-03010 Alicante, Spain.
Doce de Octubre Hospital, Avenida de Córdoba, s/n, ES-28041 Madrid, Spain.
Clínico Lozano Blesa Hospital, Avenida San Juan Bosco, 15, ES-50009 Zaragoza, Spain.
Ramon y Cajal University Hospital, Ramon y Cajal Institute for Health Research - IRYCIS, Alcala University, CIBERONC, Carretera de Colmenar Viejo, km 9.100, ES-28034 Madrid, Spain.
Maimonides Institute of Biomedical Research, IMIBIC, Spain, Reina Sofía Hospital, University of Córdoba, Spanish Cancer Network, (RTICC), Instituto de Salud Carlos III, Avenida Menéndez Pidal, s/n, ES-14004, Córdoba, Spain.
Valencia General Hospital, Avenida Tres Cruces, 2, ES-46014 Valencia, Spain.
Elche General University Hospital, Camí de l'Almazara, 11, ES-03203 Alicante, Spain.
San Carlos Hospital, Calle del Professor Martín Lagos, S/N, ES-28040 Madrid, Center affiliated to the Red Temática de Investigación Cooperativa, RD06/0020/0021, Spain, Instituto Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain.
Sabadell Hospital, Corporación Sanitaria Parc Taulí, Parc del Taulí, 1, ES-08208 Sabadell, Spain.
Jaén Hospital Complex, Av. del Ejército Español, 10, ES-23007 Jaén, Spain.
Marqués de Valdecilla Hospital, Av. de Valdecilla, s/n, ES-39008 Santander, Spain.
L´Hospitalet General Hospital, Av. Josep Molins, 29, ES-08906 L´Hospitalet de Llobregat, Spain.
A Coruña University Hospital Complex, As Xubias, 84, ES-15006 La Coruña, Spain.
Virgen de las Nieves Hospital, Av. de las Fuerzas Armadas, 2, ES-18014 Granada, Spain.



In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations.


Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 + R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT-RAS patients.


Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WT-RAS: 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab-FOLFIRI (WT-RAS: 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT-RAS: 37%/69%). The R0-R1 resection rate was 34%/46% (WT-RAS:26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: [0.6-1.5]; WT-RAS:13/15; HR: 0.7 [0.4-1.3]). Median OS was 37/41 months (HR:1.0 [0.6-1.8]; WT-RAS: 39/49; HR:0.9 [0.4-1.9]). In WT-RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS ≥ 30%/ ≥ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p = 0.003) and neuropathy (13%/0%; p = 0.025) in the Pmab-FOLFOX4 arm.


In patients with WT-KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and Pmab-FOLFIRI resulted in high ORR and ETS, allowing potentially curative resection. No significant differences in efficacy were observed between the two regimens. (


FOLFIRI; FOLFOX; First-line; Liver-limited disease; Metastatic colorectal cancer; Panitumumab; Resection

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