Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma.
PURPOSE: To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma. EXPERIMENTAL DESIGN: This phase II, open-l...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1826303728916889600 |
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| author | Kirkwood, J Bastholt, L Robert, C Sosman, J Larkin, J Hersey, P Middleton, M Cantarini, M Zazulina, V Kemsley, K Dummer, R |
| author_facet | Kirkwood, J Bastholt, L Robert, C Sosman, J Larkin, J Hersey, P Middleton, M Cantarini, M Zazulina, V Kemsley, K Dummer, R |
| author_sort | Kirkwood, J |
| collection | OXFORD |
| description | PURPOSE: To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma. EXPERIMENTAL DESIGN: This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m(2)/d for 5 days, then 23 days off-treatment). The primary endpoint was progression-free survival. RESULTS: Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86-1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (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). However, five of the six selumetinib partial responders were BRAF mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.5%), and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%), and vomiting (44.2%) were reported with temozolomide. CONCLUSIONS: No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for BRAF/NRAS mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had BRAF mutant tumors. |
| first_indexed | 2024-03-07T06:07:08Z |
| format | Journal article |
| id | oxford-uuid:ee3b9286-b320-4e02-acd7-c44cb33afa89 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:07:08Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:ee3b9286-b320-4e02-acd7-c44cb33afa892022-03-27T11:31:08ZPhase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ee3b9286-b320-4e02-acd7-c44cb33afa89EnglishSymplectic Elements at Oxford2012Kirkwood, JBastholt, LRobert, CSosman, JLarkin, JHersey, PMiddleton, MCantarini, MZazulina, VKemsley, KDummer, R PURPOSE: To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma. EXPERIMENTAL DESIGN: This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m(2)/d for 5 days, then 23 days off-treatment). The primary endpoint was progression-free survival. RESULTS: Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86-1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (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). However, five of the six selumetinib partial responders were BRAF mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.5%), and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%), and vomiting (44.2%) were reported with temozolomide. CONCLUSIONS: No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for BRAF/NRAS mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had BRAF mutant tumors. |
| spellingShingle | Kirkwood, J Bastholt, L Robert, C Sosman, J Larkin, J Hersey, P Middleton, M Cantarini, M Zazulina, V Kemsley, K Dummer, R Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. |
| title | Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. |
| title_full | Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. |
| title_fullStr | Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. |
| title_full_unstemmed | Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. |
| title_short | Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. |
| title_sort | phase ii open label randomized trial of the mek1 2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma |
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