Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicentre, randomised trial (SUMIT)

Carvajal, R. D. et al. (2018) Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicentre, randomised trial (SUMIT). Journal of Clinical Oncology, 36(12), pp. 1232-1239. (doi: 10.1200/JCO.2017.74.1090) (PMID:29528792)

Abstract

Purpose: Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods: The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial (ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m2 intravenously on day 1 of every 21- day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by blinded independent central radiologic review. Secondary end points included overall survival and objective response rate. Results: A total of 129 patients were randomly assigned to receive selumetinib plus dacarbazine (n = 97) or placebo plus dacarbazine (n = 32). In the selumetinib plus dacarbazine group, 82 patients (85%) experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine group (median, 2.8 v 1.8 months); the hazard ratio for PFS was 0.78 (95% CI, 0.48 to 1.27; two-sided P = .32). The objective response rate was 3% with selumetinib plus dacarbazine and 0% with placebo plus dacarbazine (two-sided P = .36). At 37% maturity (n = 48 deaths), analysis of overall survival gave a hazard ratio of 0.75 (95% CI, 0.39 to 1.46; two-sided P = .40). The most frequently reported adverse events (selumetinib plus dacarbazine v placebo plus dacarbazine) were nausea (62% v 19%), rash (57% v 6%), fatigue (44% v 47%), diarrhea (44% v 22%), and peripheral edema (43% v 6%). Conclusion: In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had a tolerable safety profile but did not significantly improve PFS compared with placebo plus dacarbazine.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Evans, Professor Jeff
• Authors: Carvajal, R. D., Piperno-Neumann, S., Kapiteijn, E., Chapman, P. B., Frank, S., Joshua, A. M., Pitulats, J. M., Wolter, P., Cocquyt, V., Chmielowski, B., Evans, T.R. J., Gastaud, L., Linette, G., Berking, C., Schatchter, J., Rodrigues, M. J., Shoushtari, A. N., Clemett, D., Ghiorghiu, D., Mariani, G., Spratt, S., Lovick, S., Barker, P., Kilgour, E., Lai, Z., Schwartz, G. K., and Nathan, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Clinical Oncology
• Publisher: American Society of Clinical Oncology
• ISSN: 0732-183X
• ISSN (Online): 1527-7755
• Published Online: 12 March 2018
• Copyright Holders: Copyright © 2018 American Society of Clinical Oncology
• First Published: First published in Journal of Clinical Oncology 369120;1232-1239
• Publisher Policy: Reproduced with the permission of the Publisher