ArticlePloS one2015
Analysis of BRAF and NRAS Mutation Status in Advanced Melanoma Patients Treated with Anti-CTLA-4 Antibodies: Association with Overall Survival?
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Efficacy and Safety of Apatinib in Patients with Recurrent or Refractory Melanoma.The oncologist · 2022Trial
- Association of NRAS Mutation With Clinical Outcomes of Anti-PD-1 Monotherapy in Advanced Melanoma: A Pooled Analysis of Four Asian Clinical Trials.Frontiers in immunology · 2021Trial
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial.Nature communications · 2023Article
- A real-world study of adjuvant anti-PD -1 immunotherapy on stage III melanoma with BRAF, NRAS, and KIT mutations.Cancer medicine · 2023Article
- Melanoma Targeted Therapies beyondCancers · 2021Review
- Defining and Targeting BRAF Mutations in Solid Tumors.Current treatment options in oncology · 2021Review
- Article
- Novel insights into the pathogenesis and treatment of NRAS mutant melanoma.Expert review of precision medicine and drug development · 2021Article
- Management of V600E and V600K BRAF-Mutant Melanoma.Current treatment options in oncology · 2019Review
- Role of tumor gene mutations in treatment response to immune checkpoint blockades.Precision clinical medicine · 2019Review
- Cutaneous melanoma: From pathogenesis to therapy (Review).International journal of oncology · 2018Review
- Biomarkers for Immune Checkpoint Inhibitors in Melanoma.Frontiers in oncology · 2018Review
- Metastatic melanoma patients' sensitivity to ipilimumab cannot be predicted by tumor characteristics.International journal of surgery. Oncology · 2017Article
- Targeted agents and immunotherapies: optimizing outcomes in melanoma.Nature reviews. Clinical oncology · 2017Review
- Treatment ofTherapeutic advances in medical oncology · 2017Review
- Biomarkers for Response of Melanoma Patients to Immune Checkpoint Inhibitors: A Systematic Review.Frontiers in oncology · 2017Article
- Epigallocatechin-3-gallate(EGCG) suppresses melanoma cell growth and metastasis by targeting TRAF6 activity.Oncotarget · 2016Article
- What have we learned from cancer immunotherapy in the last 3 years?Journal of translational medicine · 2014Article
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ipilimumab and tremelimumab are human monoclonal antibodies (Abs) against cytotoxic T-lymphocyte 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. The median 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). The median OS of NRAS mutated patients (n = 24) was 12.1 months and although was prolonged compared to the median OS of BRAF mutated patients (n = 38, mOS = 8.03 months) 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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