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Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial

Corrie, P.G.; Marshall, A.; Nathan, P.D.; Lorigan, P.; Gore, M.; Tahir, S.; Faust, G.; Kelly, C.G.; Marples, M.; Danson, S.J.; Marshall, E.; Houston, S.J.; Board, R.E.; Waterston, A.M.; Nobes, J.P.; Harries, M.; Kumar, S.; Goodman, A.; Dalgleish, A.; Martin-Clavijo, A.; Westwell, S.; Casasola, R.; Chao, D.; Maraveyas, A.; Patel, P.M.; Ottensmeier, C.H.; Farrugia, D.; Humphreys, A.; Eccles, B.; Young, G.; Barker, E.O.; Harman, C.; Weiss, M.; Myers, K.A.; Chhabra, A.; Rodwell, S.H.; Dunn, J.A.; Middleton, M.R.; Investigators, AVAST-M; Nathan, Paul; Lorigan, Paul; Dziewulski, Peter; Holikova, Sonja; Panwar, Udaiveer; Tahir, Saad; Faust, Guy; Thomas, Anne; Corrie, Pippa; Sirohi, Bhawna; Kelly, Charles; Middleton, Mark; Marples, Maria; Danson, Sarah; Lester, James; Marshall, Ernest; Ajaz, Mazhar; Houston, Stephen; Board, Ruth; Eaton, David; Waterston, Ashita; Nobes, Jenny; Loo, Suat; Gray, Gill; Stubbings, Helen; Gore, Martin; Harries, Mark; Kumar, Satish; Goodman, Andrew; Dalgleish, Angus;...

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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

AVAST-M Investigators

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

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



Abstract

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 (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). 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. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Journal Article Type Article
Online Publication Date Jan 6, 2020
Publication Date 2018-08
Publicly Available Date Mar 28, 2024
Journal Annals of Oncology
Print ISSN 1569-8041
Electronic ISSN 1569-8041
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 29
Issue 8
Pages 1843 -1852
DOI https://doi.org/10.1093/annonc/mdy229
Keywords ?? Adolescent ???? Adult ???? Aged ???? Aged, 80 and over ???? Bevacizumab ???? Chemotherapy, Adjuvant ???? Dermatologic Surgical Procedures ???? Disease-Free Survival ???? Drug Administration Schedule ???? Female ???? Follow-Up Studies ???? Humans ???? M
Publisher URL http://doi.org/10.1093/annonc/mdy229

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