| General information |
| Database: | DB00975 |
| Objective: | Patients with melanoma harbouring Val600 BRAF mutations benefit from treatment with BRAF inhibitors. however, no targeted treatments exist for patients with BRAF wildtype tumours, including those with NRAS mutations. They aimed to assess the use of MEK162, a smallmolecule MEK1/2 inhibitor, in patients with NRASmutated or Val600 BRAFmutated advanced melanoma. |
| Authors: | Ascierto PA, et al |
| Title: | MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a nonrandomised, openlabelphase 2 study. |
| Journal: | Lancet Oncol. |
| Year: | 2013 |
| PMID: | 23414587 |
| Trial Design |
| Clinical Trial Id: | NCT01320085 |
| Agent: | MEK162
|
| Target: | Dual specificity mitogenactivated protein kinase kinase
|
| Cancer Type: | melanoma |
| Cancer Subtype: | melanoma harbouring BRAF V600 mutations |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a nonrandomised, openlabelphase II study |
| Key Patients Feature: | patients with NRASmutated or BRAFmutated advanced melanoma; Previous treatment with BRAF inhibitors was permitted, but previous MEK inhibitor therapy was not allowed |
| Biomarker: | NRAS mutations |
| Biomark Analysis: | Six (20%) of 30 patients with NRASmutated melanoma had a partial response (three confirmed) as did eight (20%) of 41 patients with BRAFmutated melanoma (two confirmed). |
| Control Group Info: | twicedaily MEK162 45 mg for NRASmutated melanoma, twicedaily MEK162 45 mg for BRAFmutated melanoma, and twicedaily MEK162 60 mg for BRAFmutated melanoma. |
| Treatment Info: | The three arms were: twicedaily MEK162 45 mg for NRASmutated melanoma, twicedaily MEK162 45 mg for BRAFmutated melanoma, and twicedaily MEK162 60 mg for BRAFmutated melanoma. |
| Primary End Point: | the proportion of patients who had an objective response (ie, a complete response or confirmed partial response). |
| Secondary End Point: | NA |
| Patients Number: | 71 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 63% in the NRASmutated group and 21 in the BRAFmutated group. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.7 months (95% CI 2.5-5.4) for patients with NRASmutated melanoma and 3.6 months (2.0-3.8) for patients with BRAFmutated melanoma. Median PFS for the seven patients pretreated with a BRAF inhibitor was 1.7 months (1.6-2.0). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent adverse events were acneiform dermatitis (18 [60%] patients with NRAS mutated melanoma and 15 [37%] patients with the BRAFmutated melanoma), rash (six [20%] and 16 [39%]), peripheral oedema (ten [33%] and 14 [34%]), facial oedema (nine [30%] and seven [17%]), diarrhoea (eight [27%] and 15 [37%]), and creatine phosphokinase increases (11 [37%] and nine [22%]). Increased creatine phosphokinase was the most common grade 3-4 adverse event (seven [23%] and seven [17%]). Four patients had serious adverse events (two per arm), which included diarrhoea, dehydration, acneiform dermatitis, general physical deterioration, irregular heart rate, malaise, and small intestinal perforation. No deaths occurred from treatmentrelated causes. |
| Conclusions: | To our knowledge, MEK162 is the first targeted therapy to show activity in patients with NRAS mutated melanoma and might offer a new option for a cancer with few effective treatments. |