TY - JOUR
T1 - Analysis of BRAF and NRAS mutation status in advanced melanoma patients treated with anti-CTLA-4 antibodies
T2 - Association with overall survival?
AU - Mangana, Joanna
AU - Cheng, Phil F.
AU - Schindler, Katja
AU - Weide, Benjamin
AU - Held, Ulrike
AU - Frauchiger, Anna L.
AU - Romano, Emanuella
AU - Kähler, Katharina C.
AU - Rozati, Sima
AU - Rechsteiner, Markus
AU - Moch, Holger
AU - Michielin, Olivier
AU - Garbe, Claus
AU - Hauschild, Axel
AU - Hoeller, Christoph
AU - Dummer, Reinhard
AU - Goldinger, Simone M.
N1 - Publisher Copyright:
© 2015 Mangana et al.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0139438
DO - 10.1371/journal.pone.0139438
M3 - Article
C2 - 26426340
AN - SCOPUS:84947285069
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 10
M1 - e0139438
ER -