A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients
| Autor: | Elez, Elena, Pericay, Carles, Valladares-Ayerbes, Manuel, Bando, Inmaculada, Safont, Maria Jose, Gallego, Javier, Grávalos, Cristina, Arrivi, Antonio, Carrato, Alfredo, Conde, Verónica, Ortiz, Maria José, López, Carlos, Alonso, Beatriz, Ruiz de Mena, Inmaculada, Díaz-Rubio, Eduardo, Tabernero, Josep, Aranda, Enrique, Universitat Autònoma de Barcelona |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Neuroblastoma RAS viral oncogene homolog Male Cancer Research desequilibrio hidroelectrolítico Lung Neoplasms ganglios linfáticos astenia Colorectal cancer humanos Water-Electrolyte Imbalance Phases of clinical research Salvage therapy medicine.disease_cause Epiregulin GTP Phosphohydrolases proteínas protooncogénicas B-raf 0302 clinical medicine erupciones por medicamentos Antineoplastic Combined Chemotherapy Protocols Magnesium mediana edad Peritoneal Neoplasms Aged 80 and over anciano resultado del tratamiento Panitumumab protocolos de quimioterapia antineoplásica combinada Liver Neoplasms adulto Middle Aged Progression-Free Survival ErbB Receptors Survival Rate Treatment Outcome 030220 oncology & carcinogenesis Female KRAS Drug Eruptions GTP fosfohidrolasas Colorectal Neoplasms PTEN fosfohidrolasa medicine.drug Adult Diarrhea Proto-Oncogene Proteins B-raf medicine.medical_specialty neoplasias colorrectales neoplasias pulmonares neoplasias hepáticas proteínas de membranas Adenocarcinoma Irinotecan Amphiregulin Article Proto-Oncogene Proteins p21(ras) 03 medical and health sciences diarrea Internal medicine magnesio medicine Humans tasa de supervivencia neoplasms Aged Salvage Therapy business.industry PTEN Phosphohydrolase Membrane Proteins medicine.disease tratamiento de última línea proteínas protooncogénicas p21(ras) Asthenia neoplasias peritoneales Lymph Nodes business |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona British Journal of Cancer |
| Popis: | 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. This work was supported by Amgen S. A, who did not have any role in study design; collection, analysis and interpretation of data; writing the report, or the decision to submit the report for publication. |
| Databáze: | OpenAIRE |
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