A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients
Por:
Elez E, Pericay C, Valladares-Ayerbes M, Bando I, Safont MJ, Gallego J, Grávalos C, Arrivi A, Carrato A, Conde V, Ortiz MJ, López C, Alonso B, Ruiz de Mena I, Díaz-Rubio E, Tabernero J and Aranda E
Publicada:
27 ago 2019
Resumen:
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.
Filiaciones:
Elez E:
Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Pericay C:
Department of Medical Oncology, C.S. Parc Tauli, Barcelona, Spain
Valladares-Ayerbes M:
Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain
IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain
Bando I:
Laboratory Hospital Clínico San Carlos. Instituto de Investigación Hospital Clínico San Carlos (IdISSC), University Complutense, Madrid, Spain
Ciberonc, Madrid, Spain
Safont MJ:
Department of Medical Oncology, General Universitario de Valencia Hospital, Valencia, Spain
:
Department of Medical Oncology, General Universitario de Elche Hospital, Alicante, Spain
Grávalos C:
Department of Medical Oncology, Universitario Doce de Octubre Hospital, Madrid, Spain
Arrivi A:
Department of Medical Oncology, Son Llàtzer Hospital, Palma de Mallorca, Spain
Clínica Rotger, Palma, Balearic Islands, Spain
Carrato A:
Department of Medical Oncology, IRYCIS, CIBERONC, Alcalá University, Hospital Universitario Ramón y Cajal, Madrid, Spain
Conde V:
Department of Medical Oncology, Virgen de las Nieves Hospital, Granada, Spain
Ortiz MJ:
IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain
López C:
Department of Medical Oncology, Marqués de Valdecilla Hospital, Santander, Spain
Alonso B:
Department of Medical Oncology, Universitario de Canarias Hospital, Tenerife, Spain
Ruiz de Mena I:
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD), Madrid, Spain
Díaz-Rubio E:
Laboratory Hospital Clínico San Carlos. Instituto de Investigación Hospital Clínico San Carlos (IdISSC), University Complutense, Madrid, Spain
Ciberonc, Madrid, Spain
Tabernero J:
Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Aranda E:
IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain
hybrid, Green Published
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