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

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

doi:10.1093/annonc/mdy229

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

, P. G. Corrie (Lead / Corresponding author), 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. DalgleishA. 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

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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.

Original language	English
Pages (from-to)	1843-1852
Number of pages	10
Journal	Annals of Oncology
Volume	29
Issue number	8
Early online date	13 Jul 2018
DOIs	https://doi.org/10.1093/annonc/mdy229
Publication status	Published - Aug 2018

Keywords

Adjuvant therapy
Bevacizumab
Melanoma

ASJC Scopus subject areas

Hematology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/annonc/mdy229Licence: CC BY

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, 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., ... Middleton, M. R. (2018). Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial. Annals of Oncology, 29(8), 1843-1852. https://doi.org/10.1093/annonc/mdy229

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

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.",

keywords = "Adjuvant therapy, Bevacizumab, Melanoma",

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

year = "2018",

month = aug,

doi = "10.1093/annonc/mdy229",

language = "English",

volume = "29",

pages = "1843--1852",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier",

number = "8",

}

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 2018, 'Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial', Annals of Oncology, vol. 29, no. 8, pp. 1843-1852. https://doi.org/10.1093/annonc/mdy229

TY - JOUR

T1 - Adjuvant bevacizumab for melanoma patients at high risk of recurrence

T2 - survival analysis of the AVAST-M trial

AU - Corrie, P. G.

AU - Marshall, A.

AU - Nathan, P. D.

AU - Lorigan, P.

AU - Gore, M.

AU - Tahir, S.

AU - Faust, G.

AU - Kelly, C. G.

AU - Marples, M.

AU - Danson, S. J.

AU - Marshall, E.

AU - Houston, S. J.

AU - Board, R. E.

AU - Waterston, A. M.

AU - Nobes, J. P.

AU - Harries, M.

AU - Kumar, S.

AU - Goodman, A.

AU - Dalgleish, A.

AU - Martin-Clavijo, A.

AU - Westwell, S.

AU - Casasola, R.

AU - Chao, D.

AU - Maraveyas, A.

AU - Patel, P. M.

AU - Ottensmeier, C. H.

AU - Farrugia, D.

AU - Humphreys, A.

AU - Eccles, B.

AU - Young, G.

AU - Barker, E. O.

AU - Harman, C.

AU - Weiss, M.

AU - Myers, K. A.

AU - Chhabra, A.

AU - Rodwell, S. H.

AU - Dunn, J. A.

AU - Middleton, M. R.

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

KW - Adjuvant therapy

KW - Bevacizumab

KW - Melanoma

UR - http://www.scopus.com/inward/record.url?scp=85055586534&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdy229

DO - 10.1093/annonc/mdy229

M3 - Article

C2 - 30010756

SN - 0923-7534

VL - 29

SP - 1843

EP - 1852

JO - Annals of Oncology

JF - Annals of Oncology

IS - 8

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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