Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.
| Title: | Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial. |
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| Authors: | Corrie PG; Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. Electronic address: pippa.corrie@addenbrookes.nhs.uk.; Marshall A; Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.; Nathan PD; Medical Oncology, Mount Vernon Hospital, Northwood, UK.; Lorigan P; Department of Medical Oncology, Christie Hospital, Manchester, UK.; Gore M; Royal Marsden Hospital NHS Trust, London, UK.; Tahir S; Oncology Research, Broomfield Hospital, Chelmsford, UK.; Faust G; Oncology Department, Leicester Royal Infirmary, Leicester, UK.; Kelly CG; Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, Newcastle upon Tyne, UK.; Marples M; Leeds Cancer Centre, St James's University Hospital, Leeds, UK.; Danson SJ; Weston Park Hospital, Academic Unit of Clinical Oncology, Sheffield, UK.; Marshall E; Cancer & Palliative Care, St. Helen's Hospital, St. Helens, UK.; Houston SJ; Oncology Department, Royal Surrey County Hospital, Guildford, UK.; Board RE; Rosemere Cancer Centre, Royal Preston Hospital, Preston, UK.; Waterston AM; Clinical Trials Unit, Beatson WOS Cancer Centre, Glasgow, UK.; Nobes JP; Department of Clinical Oncology, Norfolk & Norwich University Hospital, Norwich, UK.; Harries M; Guy's & St. Thomas' Hospital, Guy's Cancer Centre, London, UK.; Kumar S; Velindre Cancer Centre, Cardiff, UK.; Goodman A; Exeter Oncology Centre, Royal Devon and Exeter Hospital, Exeter, UK.; Dalgleish A; St George's Hospital, Cancer Centre, London, UK.; Martin-Clavijo A; Cancer Centre, Queen Elizabeth Hospital, Birmingham, UK.; Westwell S; Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, UK.; Casasola R; Cancer Centre, Ninewells Hospital, Dundee, UK.; Chao D; Royal Free Hospital, London, UK.; Maraveyas A; Castle Hill Hospital, Cottingham, UK.; Patel PM; Academic Unit of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK.; Ottensmeier CH; CRUK and NIHR Southampton Experimental Cancer Medicine Centre, Southampton University Hospitals NHS Foundation Trust, Southampton, UK.; Farrugia D; Oncology Centre, Cheltenham General Hospital, Cheltenham, UK.; Humphreys A; Oncology Department, James Cook University Hospital, Middlesbrough, UK.; Eccles B; Oncology Department, Poole Hospital, Dorset, UK.; Young G; Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Barker EO; Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Harman C; Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Weiss M; Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Myers KA; Department of Oncology, University of Oxford, Oxford, UK; Experimental Cancer Medicine Centre, Oxford, UK.; Chhabra A; Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Rodwell SH; Melanoma Focus, Cambridge, UK.; Dunn JA; Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.; Middleton MR; Oxford NIHR Biomedical Research Centre, Oxford, UK.; 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 |
| Corporate Authors: | AVAST-M Investigators |
| Source: | Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2018 Aug 01; Vol. 29 (8), pp. 1843-1852. |
| Publication Type: | Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: England NLM ID: 9007735 Publication Model: Print Cited Medium: Internet ISSN: 1569-8041 (Electronic) Linking ISSN: 09237534 NLM ISO Abbreviation: Ann Oncol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : London : Elsevier; Original Publication: Dordrecht ; Boston : Kluwer Academic Publishers, c1990- |
| MeSH Terms: | Bevacizumab/*administration & dosage ; Melanoma/*therapy ; Neoplasm Recurrence, Local/*prevention & control ; Skin Neoplasms/*therapy; Chemotherapy, Adjuvant/methods ; Melanoma/mortality ; Melanoma/pathology ; Neoplasm Recurrence, Local/epidemiology ; Proto-Oncogene Proteins B-raf/genetics ; Skin Neoplasms/mortality ; Skin Neoplasms/pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Dermatologic Surgical Procedures ; Disease-Free Survival ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Survival Analysis ; Time Factors ; Watchful Waiting ; Young Adult |
| 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. |
| Comments: | Erratum in: Ann Oncol. 2019 Dec 1;30(12):2013-2014. doi: 10.1093/annonc/mdz237.. (PMID: 31430371) |
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| Grant Information: | 12130 United Kingdom CRUK_ Cancer Research UK; 8466 United Kingdom CRUK_ Cancer Research UK; C2195/A8466 United Kingdom CRUK_ Cancer Research UK; C7535/A6408 United Kingdom CRUK_ Cancer Research UK |
| Molecular Sequence: | ISRCTN ISRCTN 81261306; EudraCT 2006-005505-64 |
| Substance Nomenclature: | 2S9ZZM9Q9V (Bevacizumab); EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) |
| Entry Date(s): | Date Created: 20180717 Date Completed: 20191223 Latest Revision: 20250530 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC6096737 |
| DOI: | 10.1093/annonc/mdy229 |
| PMID: | 30010756 |
| Database: | MEDLINE |
Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't