Adjuvant bevacizumab as treatment for melanoma patients at high risk of recurrence: Preplanned interim results for the AVAST-M trial.

Melanoma/Skin Cancers
Session Type and Session Title: 
Oral Abstract Session, Melanoma/Skin Cancers
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr LBA9000)
Philippa Corrie, Andrea Marshall, Madusha Goonewardena, Janet A. Dunn, Mark R. Middleton, Paul D. Nathan, Martin Eric Gore, Neville Davidson, Steve Nicholson, Charles G. Kelly, Maria Marples, Sarah Danson, Ernest Marshall, Stephen Houston, Ruth E. Board, Ashita Marie Waterston, Jenny Nobes, Mark Harries, Jim Barber, Paul Lorigan; Oncology Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom; Cambridge Clinical Trials Unit, Cancer Theme, Addenbrooke's Hospital, Cambridge, United Kingdom; Churchill Hospital Cancer Center, Oxford, United Kingdom; Mount Vernon Cancer Centre, Northwood, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom; Oncology Research, Broomfield Hospital, Chelmsford, United Kingdom; Oncology Department, Leicester Royal Infirmary, Leicester, United Kingdom; Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, Newcastle upon Tyne, United Kingdom; Cancer Research, St James’s University Hospital, Leeds, United Kingdom; Cancer Research Centre, Weston Park Hospital, Sheffield, United Kingdom; Cancer & Palliative Care, St. Helens Hospital, St Helens, United Kingdom; Oncology Department, Royal Surrey County Hospital, Guildford, United Kingdom; Oncology Department, Royal Preston Hospital, Preston, United Kingdom; Clinical Trials Unit, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; Clinical Oncology, Norfolk & Norwich University Hospital, Norwich, United Kingdom; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; Velindre Cancer Centre, Cardiff, United Kingdom; Department of Medical Oncology, Christie Hospital, Withington, Manchester, United Kingdom

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Abstract Disclosures


Background: Bevacizumab (Bev) is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF) shown to improve survival in several advanced solid tumors. Multiple adjuvant trials are underway, but trials that have reported in colon and triple-negative breast cancer did not meet their primary end points. Since VEGF is a relevant target in melanoma, AVAST-M aimed to evaluate the role of Bev in patients (pts) with resected melanoma at high risk of recurrence. Methods: AVAST-M is a randomized phase III trial evaluating single agent Bev (7.5mg/kg IV 3 weekly for 1 year) as adjuvant therapy following resection of AJCC stage IIB, IIC, and III cutaneous melanoma compared to standard observation (Obs). 1,320 pts were required to detect 8% differences in 5-year overall survival (OS) rate from 40% to 48%; 85% power, 5% alpha level. Primary endpoint is OS; secondary endpoints are disease free interval (DFI), distant-metastasis free interval (DMFI), safety, and quality of life (QoL). An associated translational study is ongoing. Results of the first pre-planned interim analysis (agreed by the IDSMC) are reported here. Results: Between July 2007 and March 2012, 1,343 pts were recruited. 56% were male; median age 56 years (range 18-88 years), 16% were stage IIB, 11% IIC, 15% IIIA, 36% IIIB, 20% IIIC, and 2% unknown stage. Ulceration status of the primary melanoma was: 38% present, 45% absent, 17% unknown. At the time of the interim analysis, 286 (21%) patients had died. Median follow-up for survival was 25 months. Median duration of Bev treatment in 671 treated pts was 51 weeks (dose intensity 86%). Main outcomes are shown in the table. Grade 3/4 adverse events were experienced in 101 (15%) Bev pts and 36 (5%) Obs pts. Conclusions: Interim analysis of this large, multicenter trial of melanoma patients at high risk of recurrence has shown that adjuvant Bev monotherapy is well tolerated and improved DFI. Longer follow-up is required to determine an impact on the primary endpoint of 5-year OS. Clinical trial information: 81261306.

Bev Obs Bev Obs Bev Obs
No. of events 264 300 211 232 140 146
1-year rates 77% 70% 85% 81% 95% 94%
2-year rates 59% 57% 69% 69% 82% 82%
HR 0.83 0.88 0.97
95% CI 0.70 - 0.98 0.73 - 1.06 0.78 - 1.22
P value 0.03 0.18 0.76