The Design of a Trial Analyzing Selumetinib in Advanced Uveal Melanoma

Richard D. Carvajal, MD, medical oncologist, Memorial Sloan-Kettering Cancer Center, describes the design of a phase II study of selumetinib versus temozolomide in gnaq/Gna11 mutant uveal melanoma.

It is challenging to conduct definitive trials in rare diseases, Carvajal says, and a lot of thought went into this trial's design. The trial design required the accrual of 80 patients and allowed 120 patients with the mutation. Over the course of three years, 98 patients were accrued across 15 sites.

The primary endpoint of the trial was progression-free survival (PFS). Final data showed that PFS doubled: 7 weeks with chemotherapy compared with 15.9 weeks with selumetinib (hazard ratio = 0.46).

Clinical Pearls

There was also an increased response rate in patients treated with selumetinib, demonstrating biologic activity. Carvajal notes that about half of the patients treated with the drug experienced tumor shrinkage and 7 patients experienced major tumor shrinkage. In the context of the history of trials in this disease, response rates over 5% are very rare, Carvajal says.

• This trial accrued 98 patients across 15 sites
• PFS doubled with selumetinib vs chemotherapy
• Selumetinib increased response rate, demonstrating biologic activity with the drug