Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2018 Aug 1;29(8):1843-1852.
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  1 , A Marshall  2 , P D Nathan  3 , P Lorigan  4 , M Gore  5 , S Tahir  6 , G Faust  7 , C G Kelly  8 , M Marples  9 , S J Danson  10 , E Marshall  11 , S J Houston  12 , R E Board  13 , A M Waterston  14 , J P Nobes  15 , M Harries  16 , S Kumar  17 , A Goodman  18 , A Dalgleish  19 , A Martin-Clavijo  20 , S Westwell  21 , R Casasola  22 , D Chao  23 , A Maraveyas  24 , P M Patel  25 , C H Ottensmeier  26 , D Farrugia  27 , A Humphreys  28 , B Eccles  29 , G Young  30 , E O Barker  30 , C Harman  30 , M Weiss  30 , K A Myers  31 , A Chhabra  30 , S H Rodwell  32 , J A Dunn  2 , M R Middleton  33 ; 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, Murray Brunt, 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
Affiliations
Randomized Controlled Trial

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

P G Corrie et al. Ann Oncol. .

Erratum in

  • Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.
    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. Corrie PG, et al. Ann Oncol. 2019 Dec 1;30(12):2013-2014. doi: 10.1093/annonc/mdz237. Ann Oncol. 2019. PMID: 31430371 Free PMC article. No abstract available.

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Overall survival (A), distant metastasis-free interval (B) and disease-free interval (C), by trial arm.
Figure 2.
Figure 2.
Hazard ratio plot of the treatment effect by prognostic factors for overall survival.
Figure 3.
Figure 3.
Overall survival (A) and disease-free interval (B) by BRAF status for the observation arm patients only; Overall survival and disease-free interval by trial arm for BRAF mutant patients (C and D); Overall survival and disease-free interval by trial arm for BRAF wild type patients (E and F).
See this image and copyright information in PMC

References

    1. Hanahan D, Weinberg RA.. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646–674. - PubMed
    1. Ellis LM, Hicklin DJ.. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008; 8(8): 579–591. - PubMed
    1. Salven P, Heikkila P, Joensuu H.. Enhanced expression of vascular endothelial growth factor in metastatic melanoma. Br J Cancer 1997; 76(7): 930–934. - PMC - PubMed
    1. Ugurel S, Rappl G, Tilgen W, Reinhold U.. Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumour progression and survival. J Clin Oncol 2001; 19(2): 577–583. - PubMed
    1. Ascierto PA, Leonardi E, Ottaiano A. et al. Prognostic value of serum VEGF in melanoma patients: a pilot study. Anticancer Res 2004; 24(6): 4255–4258. - PubMed

Publication types

MeSH terms

LinkOut - more resources