Related Experiment Video
Updated: Apr 5, 2026
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma
Elizabeth I Buchbinder1, Jeffrey A Sosman2, Donald P Lawrence3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Background:
Patients with mucosal and acral melanomas have limited treatment options and a poor prognosis. Mutations of the KIT oncogene in these melanoma subtypes provide a potential therapeutic target.
Methods:
A multicenter phase 2 trial of sunitinib was conducted in patients with unresectable stage III or IV melanoma of a mucosal or acral primary origin. Patients were treated in 2 cohorts: cohort A received sunitinib at a dose of 50 mg daily for 4 weeks of a 6-week cycle, and cohort B received sunitinib at a dose of 37.5 mg daily on a continuous basis. Dose reductions were permitted for treatment-related toxicities, and tumor assessments were performed every 2 months.
Results:
Fifty-two patients were enrolled: 21 in cohort A and 31 in cohort B. Four patients had confirmed partial responses, which lasted 5 to 10 months (1 with a KIT mutation). In both cohorts, the proportion of patients alive and progression-free at 2 months was 52% (95% confidence interval, 38%-66%); this was significantly larger than the hypothesized null of 5%. There was no significant difference in response or overall survival between the 25% of patients with a KIT mutation and those without one (response rate, 7.7% vs 9.7%; overall survival, 6.4 vs 8.6 months). The overall disease control rate was 44%, and a high rate of toxicity was associated with the treatment.
Conclusions:
Sunitinib showed activity in the treatment of mucosal and acral melanoma that was not dependent on the presence of a KIT mutation. However, the medication was poorly tolerated, and there were no prolonged responses. Cancer 2015;121:4007-4015. © 2015 American Cancer Society.
Insights
Sunitinib showed limited efficacy in treating advanced mucosal and acral melanomas, with significant toxicity and no prolonged responses observed. Treatment outcomes were not influenced by KIT mutations.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Mucosal and acral melanomas present limited therapeutic options and poor prognoses.
- KIT oncogene mutations offer a potential therapeutic target in these melanoma subtypes.
Purpose of the Study:
- To evaluate the efficacy and safety of sunitinib in patients with unresectable stage III or IV mucosal or acral melanoma.
Main Methods:
- A multicenter phase 2 trial enrolled 52 patients with unresectable mucosal or acral melanoma.
- Patients received sunitinib in two cohorts with different dosing schedules.
- Tumor assessments were conducted every two months, with dose reductions allowed for toxicity.
Main Results:
- Four patients achieved partial responses lasting 5 to 10 months; one had a KIT mutation.
- Progression-free survival at 2 months was 52% in both cohorts, exceeding the hypothesized null.
- No significant difference in response or survival was observed between patients with or without KIT mutations. Overall disease control rate was 44%.
Conclusions:
- Sunitinib demonstrated activity in mucosal and acral melanoma, irrespective of KIT mutation status.
- The treatment was poorly tolerated, and prolonged responses were not achieved.
- Further research may be needed to identify more effective treatments for these melanoma types.
Related Concept Videos
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
01:24Phase II Reactions: Glucuronidation