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

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

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) 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 IV 3 weekly for 1 year) or standard observation. The primary endpoint was detection of an 8% difference in 5 year overall survival (OS) rate; secondary endpoints included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers.

Results: 1343 patients recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4 years 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). 44% 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.

Journal Article
1569-8041
Corrie, P.G.
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Nathan, P.D.
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Lorigan, P.
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Tahir, S.
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Faust, G.
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Kelly, C.G.
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Marples, M.
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Danson, S.J.
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Marshall, E.
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Houston, S.J.
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Board, R.E.
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Waterston, A.M.
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Nobes, J.P.
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Harries, M.
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Kumar, S.
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Goodman, A.
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Dalgleish, A.
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Martin-Clavijo, A.
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Westwell, S.
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Casasola, R.
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Chao, D.
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Maraveyas, A.
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Patel, P.M.
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Ottensmeier, C.H.
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Farrugia, D.
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Humphreys, A.
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Eccles, B.
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Young, G.
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Barker, E.O.
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Harman, C.
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Weiss, M.
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Myers, K.A.
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Chhabra, A.
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Rodwell, S.H.
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Dunn, J.A.
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Middleton, M.R.
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AVAST-M Investigators
Corrie, P.G.
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Nathan, P.D.
becd56a6-1824-4aff-8ea9-0846f8879a91
Lorigan, P.
42f0a90b-b129-4d62-aa8a-0463046f563b
Tahir, S.
dd2f212d-56de-4c73-95a2-eeeceeddf044
Faust, G.
40116c48-09cd-42b6-83e8-d0f22074513f
Kelly, C.G.
aa5b0c75-3d49-45fe-a148-27f76e2e1084
Marples, M.
df6d2e8c-017d-4786-930f-bbbf90c14a9a
Danson, S.J.
4e9c3bf6-9a41-4c0e-af50-02ce22e6d691
Marshall, E.
02db052f-1e6a-4e7f-8231-752b1f8a2592
Houston, S.J.
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Board, R.E.
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Waterston, A.M.
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Nobes, J.P.
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Harries, M.
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Kumar, S.
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Goodman, A.
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Dalgleish, A.
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Martin-Clavijo, A.
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Westwell, S.
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Casasola, R.
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Chao, D.
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Maraveyas, A.
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Patel, P.M.
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Ottensmeier, C.H.
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Farrugia, D.
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Humphreys, A.
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Eccles, B.
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Young, G.
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Barker, E.O.
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Harman, C.
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Weiss, M.
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Myers, K.A.
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Chhabra, A.
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Rodwell, S.H.
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Dunn, J.A.
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Middleton, M.R.
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Corrie, P.G., Nathan, P.D., Lorigan, P., 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. and Middleton, M.R. , AVAST-M Investigators (2018) Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial. Annals of Oncology. (doi:10.1093/annonc/mdy229).

Record type: Article

Abstract

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) 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 IV 3 weekly for 1 year) or standard observation. The primary endpoint was detection of an 8% difference in 5 year overall survival (OS) rate; secondary endpoints included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers.

Results: 1343 patients recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4 years 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). 44% 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.

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Accepted/In Press date: 22 June 2018
e-pub ahead of print date: 13 July 2018
Keywords: Journal Article

Identifiers

Local EPrints ID: 422557
URI: http://eprints.soton.ac.uk/id/eprint/422557
DOI: doi:10.1093/annonc/mdy229
ISSN: 1569-8041
PURE UUID: a91fdf2a-40f8-40fb-a48a-0097bd81f865

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Date deposited: 25 Jul 2018 16:30
Last modified: 15 Mar 2024 20:54

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Contributors

Author: P.G. Corrie
Author: P.D. Nathan
Author: P. Lorigan
Author: S. Tahir
Author: G. Faust
Author: C.G. Kelly
Author: M. Marples
Author: S.J. Danson
Author: E. Marshall
Author: S.J. Houston
Author: R.E. Board
Author: A.M. Waterston
Author: J.P. Nobes
Author: M. Harries
Author: S. Kumar
Author: A. Goodman
Author: A. Dalgleish
Author: A. Martin-Clavijo
Author: S. Westwell
Author: R. Casasola
Author: D. Chao
Author: A. Maraveyas
Author: P.M. Patel
Author: C.H. Ottensmeier
Author: D. Farrugia
Author: A. Humphreys
Author: B. Eccles
Author: G. Young
Author: E.O. Barker
Author: C. Harman
Author: M. Weiss
Author: K.A. Myers
Author: A. Chhabra
Author: S.H. Rodwell
Author: J.A. Dunn
Author: M.R. Middleton
Corporate Author: AVAST-M Investigators

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