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Lookup NU author(s): Dr Charles Kelly
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2018. Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n¼1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18–88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82–1.16, P ¼ 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74–0.99, P ¼ 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78–1.07, P ¼ 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P ¼ 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P ¼ 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status May predict for poorer OS untreated and potential benefit from bevacizumab.
Author(s): Corrie PG, Marshall A, Nathan PD, Lorigan P, Gore M, Tahir S, Faust G, Kelly CG, Marples M, Danson SJ, Marshall E, Houston SJ, Board RE, Waterston AM, Nobes JP, Harries M, Kumar S, Goodman A, Dalgleish A, Martin-Clavijo A, Westwell S, Casasola R, Chao D, Maraveyas A, Patel PM, Ottensmeier CH, Farrugia D, Humphreys A, Eccles B, Young G, Barker EO, Harman C, Weiss M, Myers KA, Chhabra A, Rodwell SH, Dunn JA, Middleton MR
Publication type: Article
Publication status: Published
Journal: Annals of Oncology
Print publication date: 01/08/2018
Online publication date: 13/07/2018
Acceptance date: 02/04/2018
Date deposited: 19/11/2018
ISSN (print): 0923-7534
ISSN (electronic): 1569-8041
Publisher: Oxford University Press
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