First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD)
Carrato, Alfredo (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Abad, Albert (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Massuti, Bartomeu (Hospital General Universitario de Alicante (Alacant, País Valencià))
Grávalos, Cristina (Hospital Universitario 12 de Octubre (Madrid))
Escudero, Pilar (Hospital Clínico Universitario "Lozano Blesa" de Zaragoza)
Longo Muñoz, Federico (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Manzano, José Luis (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Gómez, Auxiliadora (Instituto Maimónides de Investigación Biomédica de Córdoba)
Safont, María José (Hospital General Universitario de Valencia)
Gallego, Javier (Hospital General Universitario de Elche)
García-Paredes, Beatriz (Hospital Clínico San Carlos (Madrid))
Pericay, Carles (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Dueñas, Rosario (Complejo Hospitalario de Jaén)
Rivera, Fernando (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Losa, Ferrán (Hospital General de l'Hospitalet)
Valladares Ayerbes, Manuel (Complejo Hospitalario Universitario de A Coruña)
González, Encarnación (Hospital Universitario Virgen de las Nieves (Granada))
Aranda Aguilar, Enrique (Instituto Maimónides de Investigación Biomédica de Córdoba)
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	Abstract Background: 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. Methods: 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 þ 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. Results: Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WTRAS: 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% (WTRAS: 26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0. 9; 95% confidence interval: [0. 6e1. 5]; WT-RAS:13/15; HR: 0. 7 [0. 4 e1. 3]). Median OS was 37/41 months (HR:1. 0 [0. 6e1. 8]; WT-RAS: 39/49; HR:0. 9 [0. 4 e1. 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 Z 0. 003) and neuropathy (13%/0%; p Z 0. 025) in the Pmab-FOLFOX4 arm. Conclusions: 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. (clinicaltrials. gov:NCT00885885).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Panitumumab ; FOLFOX ; FOLFIRI ; Metastatic colorectal cancer ; First-line ; Liver-limited disease ; Resection
Published in:	European journal of cancer, Núm. 81 (2017) , p. 191-202, ISSN 1879-0852

DOI: 10.1016/j.ejca.2017.04.024

12 p, 744.6 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles