Fatal gastrointestinal toxicity with ipilimumab after BRAF/ MEK inhibitor combination in a melanoma patient achieving pathological complete response
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Maria Gonzalez-Cao1, Aram Boada2, Cristina Teixidó1,10, María Teresa Fernandez-Figueras3, Clara Mayo1,10, Francesc Tresserra4, Jean Bustamante5, Santiago Viteri1, Enrique Puertas6, Mariacarmela Santarpia7, Aldo Riso1, Feliciano Barron8, Niki Karachaliou1, Rafael Rosell1,9
1Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Dexeus University Hospital-Quirónsalud Group, Barcelona, Spain
2Dermatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
3Pathology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
4Pathology Department, Dexeus University Hospital-Quirónsalud Group, Barcelona, Spain
5Albert Einstein Medical Center, Philadelphia, PA, USA
6Radiotherapy Department, Hospital Quirónsalud, Barcelona, Spain
7Medical Oncology Unit, Human Pathology Department, University of Messina, Messina, Italy
8Medical Oncology Unit, Insituto Nacional de Cancerología, México
9Catalan Institute of Oncology, Cancer Biology & Precision Medicine Programme, Germans Trias i Pujol Hospital and Health Sciences Institute, Badalona, Spain
10Pangaea Biotech, Laboratory of Oncology, Barcelona, Spain
Maria Gonzalez-Cao, email: firstname.lastname@example.org
Keywords: BRAF mutation, ipilimumab, melanoma, sequential treatment, toxicity
Received: April 03, 2016 Accepted: May 29, 2016 Published: July 18, 2016
Approximately 50% of metastatic melanoma patients harbor BRAF mutations. Several treatment options including the combination of BRAF and MEK inhibitors (BRAF/MEKi) and immunotherapy (mainly anti CTLA-4 and anti PD-1 antibodies), have been shown to improve survival in these patients. Although preclinical data support the synergistic effect of both modalities in combination, data confirming the activity and tolerability of these combinations are not yet available in the clinical setting. Herein, we report the case of a melanoma patient treated with sequential BRAF/MEKi (dabrafenib plus trametinib) followed by the anti CTLA-4 antibody ipilimumab who achieved a pathological complete response. Unfortunately, the patient died due to fatal gastrointestinal (GI) toxicity. Analysis of the BRAFV600E mutation in circulating tumoral DNA (ctDNA) from peripheral blood samples and serial tumor tissue biopsies throughout treatment demonstrated a good correlation with clinical evolution.
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