Abstract
BackgroundBevacizumab 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 methodsPatients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5mg/kg i.v. 3 weekly for 1year) 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. ResultsPatients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56years (range 18–88years). 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 5years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82–1.16, P=0.78). At 5years, 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). ConclusionsAdjuvant 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 InformationISRCTN 81261306; EudraCT Number: 2006-005505-64
Highlights
Angiogenesis is a host-dependent hallmark of cancer [1] and vascular endothelial growth factor (VEGF) is a key driver of angiogenesis [2]
We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence
At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74–0.99, P 1⁄4 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78–1.07, P 1⁄4 0.25)
Summary
Angiogenesis is a host-dependent hallmark of cancer [1] and vascular endothelial growth factor (VEGF) is a key driver of angiogenesis [2]. Hoffman-La Roche AG, Basel, Switzerland) is a recombinant humanised monoclonal antibody to VEGF licensed for treatment of several common cancers, with modest activity reported in advanced melanoma [7]. Since VEGF is a relevant target in melanoma, we carried out a UK multicentre, open-label, randomised controlled phase III trial of adjuvant bevacizumab versus standard surveillance in patients with resected cutaneous melanoma at high risk of recurrence. 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
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