A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients
BACKGROUND: 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 patie...
| Autores: | , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Conselleria de Salut i Consum del Govern de les Illes Balears |
| Repositorio: | Docusalut |
| Idioma: | inglés |
| OAI Identifier: | oai:docusalut.com:20.500.13003/16239 |
| Acceso en línea: | https://hdl.handle.net/20.500.13003/16239 |
| Access Level: | acceso abierto |
| Palabra clave: | Colorectal Neoplasms Female Magnesium Lung Neoplasms Panitumumab Male Lymph Nodes Liver Neoplasms Membrane Proteins Progression-Free Survival Irinotecan Drug Eruptions Amphiregulin Humans GTP Phosphohydrolases Adult Aged Aged, 80 and over PTEN Phosphohydrolase Water-Electrolyte Imbalance Proto-Oncogene Proteins p21(ras) Epiregulin Asthenia Diarrhea Adenocarcinoma ErbB Receptors Antineoplastic Combined Chemotherapy Protocols Middle Aged Peritoneal Neoplasms Treatment Outcome Proto-Oncogene Proteins B-raf Salvage Therapy Survival Rate Fosfohidrolasa PTEN Anfirregulina GTP Fosfohidrolasas Resultado del Tratamiento Femenino Terapia Recuperativa Neoplasias Hepáticas Neoplasias Pulmonares Magnesio Ganglios Linfáticos Masculino Persona de Mediana Edad Neoplasias Peritoneales Astenia Protocolos de Quimioterapia Combinada Antineoplásica Diarrea Irinotecán Supervivencia sin Progresión Neoplasias Colorrectales Desequilibrio Hidroelectrolítico Tasa de Supervivencia Proteínas de la Membrana Receptores ErbB Proteínas Proto-Oncogénicas B-raf Erupciones por Medicamentos Humanos Epirregulina Anciano Anciano de 80 o más Años Proteínas Proto-Oncogénicas p21(ras) Adulto |
| Sumario: | BACKGROUND: 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. METHODS: KRAS exon-2 wild-type patients failing prior irinotecan received panitumumab (6 mg/kg) and irinotecan (180 mg/m(2)) 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. RESULTS: 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). CONCLUSIONS: 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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