Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma.
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.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Elizabeth I
EI
Buchbinder
Hematology-Oncology, Vanderbilt University, Nashville, Tennessee.
Jeffrey A
JA
Sosman
Hematology-Oncology, Massachusetts General Hospital, Boston, Massachusetts.
Donald P
DP
Lawrence
Hematology-Oncology, Beth Israel-Deaconess Medical Center, Boston, Massachusetts.
David F
DF
McDermott
Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Nikhil H
NH
Ramaiya
Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
Annick D
AD
Van den Abbeele
Hematology-Oncology, Washington University in St. Louis, St. Louis, Missouri.
Gerald P
GP
Linette
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Anita
A
Giobbie-Hurder
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
F Stephen
FS
Hodi
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D009092:Mucous Membrane / Q000473:pathology; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000077210:Sunitinib
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib
KIT; acral melanoma; mucosal melanoma; sunitinib; vascular endothelial growth factor (VEGF)