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. Dalgleish & 19 others 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

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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 languageEnglish
    Pages (from-to)1843-1852
    Number of pages10
    JournalAnnals of Oncology
    Volume29
    Issue number8
    Early online date13 Jul 2018
    DOIs
    Publication statusPublished - Aug 2018

    Fingerprint

    Survival Analysis
    Melanoma
    Recurrence
    Observation
    Survival
    Confidence Intervals
    Mutation
    Bevacizumab
    Neoplasm Metastasis
    Antibodies, Monoclonal, Humanized
    Vascular Endothelial Growth Factor A
    Neoplasms
    Survival Rate
    Clinical Trials
    Skin

    Keywords

    • Adjuvant therapy
    • Bevacizumab
    • Melanoma

    Cite this

    , Corrie, P. G., Marshall, A., Nathan, P. D., Lorigan, P., Gore, M., ... 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
    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. / Adjuvant bevacizumab for melanoma patients at high risk of recurrence : survival analysis of the AVAST-M trial. In: Annals of Oncology. 2018 ; Vol. 29, No. 8. pp. 1843-1852.
    @article{f1b7ebfbf0ce414da8f2bc5ce757a69a,
    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.}",
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    doi = "10.1093/annonc/mdy229",
    language = "English",
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    pages = "1843--1852",
    journal = "Annals of Oncology",
    issn = "0923-7534",
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    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

    Adjuvant bevacizumab for melanoma patients at high risk of recurrence : survival analysis of the AVAST-M trial. /; Corrie, P. G. (Lead / Corresponding author); 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.

    In: Annals of Oncology, Vol. 29, No. 8, 08.2018, p. 1843-1852.

    Research output: Contribution to journalArticle

    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

    VL - 29

    SP - 1843

    EP - 1852

    JO - Annals of Oncology

    JF - Annals of Oncology

    SN - 0923-7534

    IS - 8

    ER -