Analysis of BRAF and NRAS mutation status in advanced melanoma patients treated with anti-CTLA-4 antibodies: Association with overall survival?

Joanna Mangana, Phil F. Cheng, Katja Schindler, Benjamin Weide, Ulrike Held, Anna L. Frauchiger, Emanuella Romano, Katharina C. Kähler, Sima Rozati, Markus Rechsteiner, Holger Moch, Olivier Michielin, Claus Garbe, Axel Hauschild, Christoph Hoeller, Reinhard Dummer, Simone M. Goldinger

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19 Scopus citations


Ipilimumab and tremelimumab are humanmonoclonal antibodies (Abs) against cytotoxic Tlymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival in advanced melanoma patients. Currently, there is no proven association between the BRAFV600 mutation and the disease control rate in response to ipilimumab. This analysis was carried out to assess if BRAFV600 and NRAS mutation status affects the clinical outcome of anti-CTLA-4-treated melanoma patients. This is a retrospective multi-center analysis of 101 patients, with confirmed BRAF and NRAS mutation status, treated with anti- CTLA-4 antibodies from December 2006 until August 2012. Themedian overall survival, defined from the treatment start date with the anti-CTLA-4. Abs-treatment to death or till last follow up, of BRAFV600 or NRAS mutant patients (n = 62) was 10.12 months (95% CI 6.78- 13.2) compared to 8.26 months (95% CI 6.02-19.9) in BRAFV600/NRASwt subpopulation (n = 39) (p = 0.67). Themedian OS of NRAS mutated patients (n = 24) was 12.1 months and although was prolonged compared to themedian OS of BRAFmutated patients (n = 38, mOS = 8.03months) or BRAFV600/NRASwt patients (n = 39, mOS = 8.26 months) the difference didn't reach statistical significance (p = 0.56). 69 patients were able to complete 4 cycles of anti-CTLA-4 treatment. Of the 24 patients treated with selected BRAF- or MEK-inhibitors, 16 patients received anti-CTLA 4 Abs following either a BRAF or MEK inhibitor with only 8 of them being able to finish 4 cycles of treatment. Based on our results, there is no difference in the median OS in patients treated with anti-CTLA-4 Abs implying that the BRAF/NRAS mutation status alone is not sufficient to predict the outcome of patients treated with anti-CTLA-4 Abs.

Original languageEnglish (US)
Article numbere0139438
JournalPloS one
Issue number10
StatePublished - Oct 1 2015
Externally publishedYes

ASJC Scopus subject areas

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