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Selumetinib effective against melanoma of the eye

Radha Chitale
4 years ago

A novel kinase inhibiting agent was the first to effectively shrink tumors in patients with uveal melanoma, a rare eye cancer, and could become the standard of care for such patients, according to results from a phase II study.

“There has been no effective systemic therapy for metastatic uveal melanoma,” said lead author Dr. Richard Carvajal of the Memorial Sloan-Kettering Cancer Center in New York, New York, US.

Out of 98 patients with metastatic melanoma of the eye, 48 were randomized to receive selumetinib and 50 received temozolomide, the standard skin melanoma chemotherapy. Fifty-percent of patients in the selumetinib group experienced tumor shrinkage, with 15 percent experiencing major shrinkage – defined as being at least 30 percent reduced tumor volume. [Abstract CRA9003]

None of the patients in the temozolomide group demonstrated significant shrinkage.

Progression-free survival, the primary endpoint, doubled with selumetinib – 15.9 weeks compared with 7.0 weeks on temozolomide (p=0.0003). Patients on temozolomide could cross over to selumetinib upon progression and 80 percent did so.

Overall survival was unaffected by selumetinib – 10.8 months compared with 9.4 months on temozolomide (p=0.4).

“This study is the first to ever demonstrate efficacy of any systemic therapy in patients with metastatic uveal melanoma,” Carvajal said.

Metastatic melanoma of the eye is an orphan disease distinct from cutaneous melanoma. The researchers said just 2,000 cases are diagnosed in the US annually and these patients have limited treatment options. The current standard of care is entry into a clinical trial.

Selumetinib inhibits a molecule in MEK signalling pathways that activate oncologic cell growth. In uveal melanoma, this type of cell growth is often triggered by mutations in Gnaq and Gna11 genes. Eighty-four percent of patients in the study population had Gnaq or Gna11 mutations.

Selumetnib may also be useful in treating other cancers that rely on MEK signalling such as cancers of the thyroid and lungs.

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