Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial
Authors: P.G. Corrie, A. Marshall, P.D. Nathan, P. Lorigan, M. Gore, S. Tahir, G. Faust, C.G. Kelly, M. Marples, S.J. Danson, E. Marshall, S.J. Houston, R.E. Board, A.M. Waterston, J.P. Nobes, M. Harries, S. Kumar, A. Goodman, A. Dalgleish, A. Martin-Clavijo, S. Westwell, R. Casasola, D. Chao, A. Maraveyas, P.M. Patel, C.H. Ottensmeier, D. Farrugia, A. Humphreys, B. Eccles, G. Young, E.O. Barker, C. Harman, M. Weiss, K.A. Myers, A. Chhabra, S.H. Rodwell, J.A. Dunn, M.R. Middleton, Paul Nathan, Paul Lorigan, Peter Dziewulski, Sonja Holikova, Udaiveer Panwar, Saad Tahir, Guy Faust, Anne Thomas, Pippa Corrie, Bhawna Sirohi, Charles Kelly, Mark Middleton, Maria Marples, Sarah Danson, James Lester, Ernest Marshall, Mazhar Ajaz, Stephen Houston, Ruth Board, David Eaton, Ashita Waterston, Jenny Nobes, Suat Loo, Gill Gray, Helen Stubbings, Martin Gore, Mark Harries, Satish Kumar, Andrew Goodman, Angus Dalgleish, Agustin Martin-Clavijo, Jerry Marsden, Sarah Westwell, Richard Casasola, David Chao, Anthony Maraveyas, Ernest Marshall, Poulam Patel, Christian Ottensmeier, David Farrugia, Alison Humphreys, Bryony Eccles, Renata Dega, Chris Herbert, Christopher Price, Murray Brunt, Martin Scott-Brown, Joanna Hamilton, Richard Larry Hayward, John Smyth, Pamela Woodings, Neena Nayak, Lorna Burrows, Virginia Wolstenholme, John Wagstaff, Marianne Nicolson, Andrew Wilson, Clare Barlow, Christopher Scrase, Timothy Podd, Michael Gonzalez, John Stewart, Martin Highley, Virginia Wolstenholme, Simon Grumett, Andrew Goodman, Toby Talbot, Kannon Nathan, Robert Coltart, Bruce Gee, Martin Gore, David Farrugia, Agustin Martin-Clavijo, Jerry Marsden, Christopher Price, David Farrugia, Kannon Nathan, Robert Coltart, Kannon Nathan, Robert Coltart
Journal: Annals of Oncology (2018)

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 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.Patients (n=1343) 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 = 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 = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 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 = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21).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.ISRCTN 81261306; EudraCT Number: 2006-005505-64.