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

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 irinoteca...

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Detalles Bibliográficos
Autores: Carrato, Alfredo|||0000-0001-7749-8140, Abad, Albert, Massuti, Bartomeu|||0000-0002-6247-4493, Grávalos, Cristina|||0000-0001-9239-6505, Escudero, Pilar, Longo Muñoz, Federico, Manzano Mozo, Jose Luis|||0000-0002-8987-4577, Gómez, Auxiliadora, Safont, María José, Gallego Plazas, Javier|||0000-0002-0584-1242, García Paredes, Beatriz|||0000-0003-3562-1600, Pericay, Carles|||0000-0002-4975-7851, Dueñas, Rosario, Rivera, Fernando|||0000-0001-8915-226X, Losa, Ferrán, Valladares Ayerbes, Manuel, González, Encarnación, Aranda Aguilar, Enrique|||0000-0002-5471-2842
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:196522
Acceso en línea:https://ddd.uab.cat/record/196522
https://dx.doi.org/urn:doi:10.1016/j.ejca.2017.04.024
Access Level:acceso abierto
Palabra clave:Panitumumab
FOLFOX
FOLFIRI
Metastatic colorectal cancer
First-line
Liver-limited disease
Resection
Descripción
Sumario: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).

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