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Lookup NU author(s): Professor Ruth Plummer
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The AuthorsAims: The MAPK pathway is constitutively activated in uveal melanoma (UM). Selumetinib (AZD6244, ARRY-142886), a MEK inhibitor, has shown limited activity as monotherapy in metastatic UM. Pre-clinical studies support synergistic cytotoxic activity for MEK inhibitors combined with taxanes, and here we sought to assess the clinical efficacy of combining selumetinib and paclitaxel. Patients and methods: Seventy-seven patients with metastatic UM who had not received prior chemotherapy were randomised to selumetinib alone, or combined with paclitaxel with or without interruption in selumetinib two days before paclitaxel. The primary endpoint was progression free survival (PFS). After amendment, the combination arms were combined for analysis and the sample size adjusted to detect a hazard ratio (HR): 0.55, 80% power at 1-sided 5% significance level. Results: The median PFS in the combination arms was 4.8 months (95% CI: 3.8 - 5.6) compared with 3.4 months (2.0 - 3.9) in the selumetinib arm (HR 0.62 [90% CI 0.41 - 0.92], 1-sided p-value = 0.022). ORR was 14% and 4% in the combination and monotherapy arms respectively. Median OS was 9 months for the combination and was not significantly different from selumetinib alone (10 months) with HR of 0.98 [90% CI 0.58 - 1.66], 1-sided p-value = 0.469. Toxicity was in keeping with the known profiles of the agents involved. Conclusions: SelPac met its primary endpoint, demonstrating an improvement in PFS for combination selumetinib and paclitaxel. No improvement in OS was observed, and the modest improvement in PFS is not practice changing.
Author(s): Sacco JJ, Jackson R, Corrie P, Danson S, Evans TRJ, Ochsenreither S, Kumar S, Goodman A, Larkin J, Karydis I, Steven N, Lorigan P, Plummer R, Patel P, Psarelli E, Olsson-Brown A, Shaw H, Leyvraz S, Handley L, Rawcliffe C, Nathan P
Publication type: Article
Publication status: Published
Journal: European Journal of Cancer
Year: 2024
Volume: 202
Online publication date: 09/03/2024
Acceptance date: 04/03/2024
Date deposited: 09/04/2024
ISSN (print): 0959-8049
ISSN (electronic): 1879-0852
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.ejca.2024.114009
DOI: 10.1016/j.ejca.2024.114009
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