| General information |
| Database: | DB00980 |
| Objective: | To compare the efficacy and tolerability of the mitogenactivated protein (MAP)/extracellular signalregulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapynaive patients with unresectable stage III/IV melanoma. |
| Authors: | Kirkwood JM, et al |
| Title: | Phase II, openlabel, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22048237 |
| Trial Design |
| Clinical Trial Id: | NCT00338130 |
| Agent: | selumetinib
|
| Target: | Dual specificity mitogenactivated protein kinase kinase
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II, openlabel, randomized trial |
| Key Patients Feature: | chemotherapynaive patients with unresectable stage III/IV melanoma |
| Biomarker: | BRAF mutations |
| Biomark Analysis: | Among patients with BRAF mutations, objective responses were similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). however, five of the six selumetinib partial responders were BRAF mutated. |
| Control Group Info: | selumetinib as monotherapy versus temozolomide |
| Treatment Info: | 100 mg oral selumetinib twice daily in 28day cycles versus oral temozolomide (200 mg/m(2)/d for 5 days, then 23 days offtreatment). |
| Primary End Point: | progression free survival. |
| Secondary End Point: | NA |
| Patients Number: | 200 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 5.8% patients receiving selumetinib and 9.4% patients in the temozolomide group. Among patients with BRAF mutations, objective responses were similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.861.32). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent SAEs in the selumetinib group were diarrhea (n = 3), vomiting (n = 3), and infections (n = 3). Small intestinal obstruction (n = 2) and confusional state (n = 2) were the most frequent SAEs in the temozolomide group. |
| Conclusions: | No significant difference in progression free survival was observed bettheyen patients with unresectable stage IIIIV melanoma unselected for BRAFNRAS mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had BRAF mutant tumors |