CHICAGO — Selumetinib decreased tumor size in 50% of patients with metastatic uveal melanoma and was associated with a twofold increased PFS when compared with temozolomide, according to phase 2 study results presented at the ASCO Annual Meeting.
“This study is the first to ever demonstrate efficacy for any systemic therapy in patients with metastatic uveal melanoma,” Richard D. Carvajal, MD, medical oncologist at Memorial Sloan-Kettering Cancer Center, said during a press conference. “Selumetinib could be considered a new standard for patients with uveal melanoma and provides a platform for the development of new combinatorial therapeutic approaches.”
About 2,000 new cases of uveal melanoma are diagnosed annually in the United States. The standard therapy for skin melanoma, temozolomide (Temodar, Schering-Plough), has shown little effect on uveal melanoma. Therefore, no known effective systemic therapy exists for these patients.
Gnaq and Gna11 alterations, which occur in 85% of patients with uveal melanoma, activate the MAPK pathway and fuels cell growth. Selumetinib blocks the MEK protein, a key component of the MAPK pathway, according to background information provided by the researchers.
For the multicenter, randomized study, Carvajal and colleagues randomly assigned 98 patients with uveal melanoma to selumetinib (n=48) or temozolomide (n=50).
All tumors were tested for mutations at baseline. Thirty-seven percent of patients had a Gnaq mutation, 44% had Gna11 mutations and 19% had an Exon 5 wild-type mutation.
Randomization was stratified according to mutation status, extent of disease and number of prior therapies.
PFS served as the primary outcome measure. Secondary outcome measures were response rate and OS.
Median PFS was 15.9 weeks among patients assigned to selumetinib compared with 7 weeks for patients assigned to temozolomide (HR=0.46; P=.0003). Median OS was 10.8 months with selumetinib vs. 9.4 months with temozolomide (P=.4).
Tumor shrinkage occurred in 50% of patients assigned to selumetinib vs. 11% of patients assigned to temozolomide. Fifteen percent of patients in the selumetinib arm achieved significant tumor shrinkage, whereas no patients in the temozolomide arm achieved significant tumor shrinkage.
“This is quite remarkable because radiographic shrinkage in this disease is quite uncommon,” Carvajal said. “In fact, if you look at previously published studies, response rates are less than 5%.”
For more information:
Carvajal RD. Abstract #CRA9003. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.
Disclosure: The study was supported in part by the Conquer Cancer Foundation of ASCO Career Development Award, the NIH, Cycle for Survival and the Fund for Ophthalmic Knowledge.