In patients with advanced uveal melanoma, treatment with the agent selumetinib, compared with chemotherapy, resulted in an improved cancer progression-free survival time and tumor response rate, but no improvement in overall survival, according to a study in the June 18 issue of JAMA. The modest improvement in clinical outcomes was accompanied by a high rate of adverse events.
Uveal melanoma arises from melanocytes within the choroid layer of the eye. There are about 1,500 new cases of uveal melanoma per year in the U.S., which is biologically distinct from skin related melanoma. Selumetinib is an oral agent that may help to inhibit the growth of cancer cells by blocking MEK1/2. A subgroup analysis from an earlier trial that included 20 patients with uveal melanoma suggested favorable results with selumetinib treatment, according to background information in the article.
Richard D. Carvajal, M.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues randomly assigned patients with metastatic uveal melanoma to receive selumetinib (n = 50; orally twice daily), or chemotherapy (n = 51; temozolomide, orally daily for 5 of every 28 days, or dacarbazine, intravenously every 21 days) until disease progression, death, intolerable adverse effects, or withdrawal of consent. After analysis of the primary outcome, 19 additional patients were registered and 18 treated with selumetinib without randomization, to complete the planned 120-patient enrollment.
The researchers reported that the median progression-free survival time was 7 weeks in the chemotherapy group (median treatment duration, 8 weeks) and 15.9 weeks in the selumetinib group (median treatment duration, 16.1 weeks). The 4-month progression-free survival rate was 8.5 percent with chemotherapy, and 43.1 percent with selumetinib. Median overall survival time was 9.1 months with chemotherapy and 11.8 months with selumetinib, a difference that was not statistically significant.
Tumor regression was uncommon with chemotherapy, whereas 49 percent of patients randomized to selumetinib achieved tumor regression. Treatment-related adverse events were observed in 97 percent of patients treated with selumetinib, with 37 percent requiring at least 1 dose reduction.
“In this hypothesis-generating study of patients with advanced uveal melanoma, selumetinib compared with chemotherapy resulted in a modestly improved progression-free survival time and rate of response; however, no improvement in overall survival was observed. Improvement in clinical outcomes was accompanied by a high rate of adverse events.” the authors conclude.
- Richard D. Carvajal, Jeffrey A. Sosman, Jorge Fernando Quevedo, Mohammed M. Milhem, Anthony M. Joshua, Ragini R. Kudchadkar, Gerald P. Linette, Thomas F. Gajewski, Jose Lutzky, David H. Lawson, Christopher D. Lao, Patrick J. Flynn, Mark R. Albertini, Takami Sato, Karl Lewis, Austin Doyle, Kristin Ancell, Katherine S. Panageas, Mark Bluth, Cyrus Hedvat, Joseph Erinjeri, Grazia Ambrosini, Brian Marr, David H. Abramson, Mark Andrew Dickson, Jedd D. Wolchok, Paul B. Chapman, Gary K. Schwartz. Effect of Selumetinib vs Chemotherapy on Progression-Free Survival in Uveal Melanoma. JAMA, 2014; 311 (23): 2397 DOI: 10.1001/jama.2014.6096
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