Fatal gastrointestinal toxicity with ipilimumab after BRAF/MEK inhibitor combination in a melanoma patient achieving pathological complete response

Maria Gonzalez-Cao, Aram Boada, Cristina Teixidó, María Teresa Fernandez-Figueras, Clara Mayo, Francesc Tresserra, Jean Bustamante, Santiago Viteri, Enrique Puertas, Mariacarmela Santarpia, Aldo Riso, Feliciano Barron, Niki Karachaliou, Rafael Rosell

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)56619-56627
Number of pages9
JournalOncotarget
Volume7
Issue number35
DOIs
Publication statusPublished - 2016

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Keywords

  • BRAF mutation
  • Ipilimumab
  • Melanoma
  • Sequential treatment
  • Toxicity

ASJC Scopus subject areas

  • Oncology

Cite this

Gonzalez-Cao, M., Boada, A., Teixidó, C., Fernandez-Figueras, M. T., Mayo, C., Tresserra, F., Bustamante, J., Viteri, S., Puertas, E., Santarpia, M., Riso, A., Barron, F., Karachaliou, N., & Rosell, R. (2016). Fatal gastrointestinal toxicity with ipilimumab after BRAF/MEK inhibitor combination in a melanoma patient achieving pathological complete response. Oncotarget, 7(35), 56619-56627. https://doi.org/10.18632/oncotarget.10651