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MEK inhibitors for pre-treated, NRAS-mutated metastatic melanoma: A multi-centre, retrospective study
Martin Salzmann1, Johannes Pawlowski2, Carmen Loquai2
1Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
Background:
MEK inhibitors (MEKi) have shown clinical efficacy for NRAS-mutated, metastasized melanoma in randomised controlled trials, yet their clinical use is currently restricted to advanced, pre-treated patients, which is a different situation compared to previous trials. Data on their efficacy in the current real-world use are scarce.
Methods:
In this retrospective, multi-centre study, we evaluated the clinical course of disease of patients treated with MEKi with at least one previous treatment line in five German cancer centres.
Results:
Thirty-three patients were included, 19 males (58%) and 14 females (42%), with a median age of 64 years. Ninety-one percent of patients were pre-treated with immune checkpoint inhibitors, 90% of patients had elevated serum lactate dehydrogenase (LDH) levels at treatment initiation, 33% suffered from cerebral metastases and 30% had an Eastern Cooperative Oncology Group performance status of 2 or higher. The response rate was 18.2%; the disease control rate was 48.5%. Median progression-free survival was 2.8 months (95% confidence interval (CI): 1.6-3.9 months), and median overall survival was 7.1 months (95% CI: 5.8-8.3 months). In subgroup analysis, clinical efficacy was similar also in patients with high LDH levels and cerebral metastases, and there was a better outcome in males and in patients treated with trametinib vs. other MEKi, which may be based on selection bias. Overall, the clinical efficacy was similar compared to previous clinical trials in earlier treatment lines.
Conclusions:
MEKi fulfil the need for an in-between treatment to stabilise the course of disease in advanced NRAS-mutated melanoma, but expectations regarding ongoing tumour response should be tempered.
Insights
MEK inhibitors (MEKi) offer a valuable treatment for advanced NRAS-mutated melanoma, showing similar efficacy in real-world use as in trials. While they help stabilize disease, significant tumor response expectations should be managed.
Area of Science:
- Oncology
- Medical Research
- Pharmacology
Background:
- MEK inhibitors (MEKi) demonstrate clinical efficacy in NRAS-mutated, metastatic melanoma.
- Current clinical use of MEKi is limited to advanced, pre-treated patients, differing from prior trial settings.
- Real-world data on MEKi efficacy in this patient population are scarce.
Purpose of the Study:
- To evaluate the clinical outcomes of MEK inhibitor treatment in advanced NRAS-mutated melanoma patients with prior treatment lines.
- To assess the real-world effectiveness of MEK inhibitors in a German cohort.
- To compare efficacy in subgroups with specific clinical characteristics.
Main Methods:
- Retrospective, multi-center study across five German cancer centers.
- Inclusion of 33 patients with NRAS-mutated, metastatic melanoma treated with MEKi after at least one prior line of therapy.
- Analysis of patient demographics, treatment history, clinical characteristics, response rates, progression-free survival, and overall survival.
Main Results:
- The study included 33 patients (58% male, median age 64), with high rates of prior immune checkpoint inhibitor treatment (91%), elevated LDH (90%), and cerebral metastases (33%).
- Response rate was 18.2%, disease control rate was 48.5%. Median progression-free survival was 2.8 months, and median overall survival was 7.1 months.
- Efficacy remained similar in subgroups with high LDH and cerebral metastases; males and trametinib-treated patients showed better outcomes, potentially due to selection bias.
Conclusions:
- MEK inhibitors serve as an important "in-between" treatment to stabilize advanced NRAS-mutated melanoma.
- Clinical efficacy in real-world settings aligns with previous trial data.
- Manage expectations for sustained tumor response; MEKi are primarily for disease stabilization.
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