Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.
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Date
2018-08ICR Author
Author
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
AVAST-M Investigators
Nathan, P
Lorigan, P
Dziewulski, P
Holikova, S
Panwar, U
Tahir, S
Faust, G
Thomas, A
Corrie, P
Sirohi, B
Kelly, C
Middleton, M
Marples, M
Danson, S
Lester, J
Marshall, E
Ajaz, M
Houston, S
Board, R
Eaton, D
Waterston, A
Nobes, J
Loo, S
Gray, G
Stubbings, H
Gore, M
Harries, M
Kumar, S
Goodman, A
Dalgleish, A
Martin-Clavijo, A
Marsden, J
Westwell, S
Casasola, R
Chao, D
Maraveyas, A
Marshall, E
Patel, P
Ottensmeier, C
Farrugia, D
Humphreys, A
Eccles, B
Dega, R
Herbert, C
Price, C
Brunt, M
Scott-Brown, M
Hamilton, J
Hayward, RL
Smyth, J
Woodings, P
Nayak, N
Burrows, L
Wolstenholme, V
Wagstaff, J
Nicolson, M
Wilson, A
Barlow, C
Scrase, C
Podd, T
Gonzalez, M
Stewart, J
Highley, M
Wolstenholme, V
Grumett, S
Goodman, A
Talbot, T
Nathan, K
Coltart, R
Gee, B
Gore, M
Farrugia, D
Martin-Clavijo, A
Marsden, J
Price, C
Farrugia, D
Nathan, K
Coltart, R
Nathan, K
Coltart, R
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
AVAST-M Investigators
Humans
Melanoma
Skin Neoplasms
Neoplasm Recurrence, Local
Proto-Oncogene Proteins B-raf
Neoplasm Staging
Disease-Free Survival
Chemotherapy, Adjuvant
Drug Administration Schedule
Survival Analysis
Follow-Up Studies
Mutation
Time Factors
Adolescent
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Young Adult
Watchful Waiting
Dermatologic Surgical Procedures
Bevacizumab
Language
eng
License start date
2018-08
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2018, 29 (8), pp. 1843 - 1852
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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