A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients

Targeted agents are standard treatment for RAS wild-type metastatic colorectal cancer in the first- and second-line settings. This phase 2 study determined the benefit of targeting the epidermal growth factor receptor (EGFR) with panitumumab plus irinotecan in irinotecan-refractory patients. KRAS ex...

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Detalles Bibliográficos
Autores: Elez, Elena|||0000-0002-4653-6324, Pericay, Carles|||0000-0002-4975-7851, Valladares-Ayerbes, Manuel, Bando, Inmaculada, Safont, Maria Jose, Gallego, Javier, Grávalos, Cristina|||0000-0001-9239-6505, Arrivi, Antonio, Carrato, Alfredo|||0000-0001-7749-8140, Conde, Verónica, Ortiz, Maria José, López, Carlos, Alonso, Beatriz, Ruiz de Mena, Inmaculada, Díaz-Rubio, Eduardo, Tabernero, Josep|||0000-0002-2495-8139, Aranda Aguilar, Enrique|||0000-0002-5471-2842
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:226563
Acceso en línea:https://ddd.uab.cat/record/226563
https://dx.doi.org/urn:doi:10.1038/s41416-019-0537-z
Access Level:acceso abierto
Palabra clave:Colorectal cancer
Oncology
Descripción
Sumario:Targeted agents are standard treatment for RAS wild-type metastatic colorectal cancer in the first- and second-line settings. This phase 2 study determined the benefit of targeting the epidermal growth factor receptor (EGFR) with panitumumab plus irinotecan in irinotecan-refractory patients. KRAS exon-2 wild-type patients failing prior irinotecan received panitumumab (6 mg/kg) and irinotecan (180 mg/m²) every 2 weeks. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). KRAS exon-2 status was evaluated centrally, along with NRAS, BRAF mutations, epiregulin, amphiregulin, PTEN and EGFR copy number status, and correlated with efficacy. Sixty-one patients were treated. Among the 46 wild-type RAS patients, the ORR was 15.2% (seven partial responses), with median PFS of 3.8 months (95% CI 2.7-4.3) and median OS of 12.5 months (95% CI 6.7-15.9). Wild-type BRAF patients showed a 13.0% response rate. No significant correlations between response and baseline biomarker expression were identified. Common grade 3-4 adverse events were diarrhoea and rash (18.0% each), hypomagnesaemia and asthenia (8.2% each). The addition of panitumumab to irinotecan as salvage therapy is feasible but has limited activity in irinotecan-refractory metastatic colorectal cancer. No biomarkers predictive of response were identified.

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