Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study
| العنوان: | Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study |
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| المؤلفون: | Stephen Houston, Andrea Marshall, Charles Kelly, Neville Davidson, Paul Lorigan, Mark R. Middleton, Martin Gore, Satish Kumar, Mark Harries, Paul Nathan, Sarah Danson, Maria Marples, Ruth E Board, Steve Nicholson, Ernest Marshall, Pippa Corrie, Jenny Nobes, Ashita Waterston, Gemma Young, Janet A. Dunn |
| المصدر: | The Lancet Oncology. 15(6):620-630 |
| بيانات النشر: | Elsevier BV, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Skin Neoplasms, Adolescent, Bevacizumab, Phases of clinical research, Antineoplastic Agents, Kaplan-Meier Estimate, Antibodies, Monoclonal, Humanized, Disease-Free Survival, law.invention, RC0254, Young Adult, Randomized controlled trial, Risk Factors, law, Internal medicine, medicine, Clinical endpoint, Humans, Adverse effect, Melanoma, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Middle Aged, Interim analysis, Surgery, Tolerability, Oncology, Chemotherapy, Adjuvant, Female, Neoplasm Recurrence, Local, business, medicine.drug |
| الوصف: | SummaryBackgroundBevacizumab, a monoclonal antibody that targets VEGF, has shown restricted activity in patients with advanced melanoma. We aimed to assess the role of bevacizumab as adjuvant treatment for patients with resected melanoma at high risk of recurrence. We report results from the preplanned interim analysis.MethodsWe did a multicentre, open-label, randomised controlled phase 3 trial at 48 centres in the UK between July 18, 2007, and March 29, 2012. Patients aged 16 years or older with American Joint Committee on Cancer stage (AJCC) stage IIB, IIC, and III cutaneous melanoma were randomly allocated (1:1), via a central, computer-based minimisation procedure, to receive intravenous bevacizumab 7·5 mg/kg, every 3 weeks for 1 year, or to observation. Randomisation was stratified by Breslow thickness of the primary tumour, N stage according to AJCC staging criteria, ulceration of the primary tumour, and patient sex. The primary endpoint was overall survival; secondary endpoints included disease-free interval, distant-metastases interval and quality of life. Analysis was by intention-to-treat. This trial is registered as an International Standardised Randomised Controlled Trial, number ISRCTN81261306.Findings1343 patients were randomised to either the bevacizumab group (n=671) or the observation group (n=672). Median follow-up was 25 months (IQR 16–37) in the bevacizumab group and 25 months (17–37) in the observation group. At the time of interim analysis, 286 (21%) of 1343 enrolled patients had died: 140 (21%) of 671 patients in the bevacizumab group, and 146 (22%) of 672 patients in the observation group. 134 (96%) of patients in the bevacizumab group died because of melanoma versus 139 (95%) in the observation group. We noted no significant difference in overall survival between treatment groups (hazard ratio [HR] 0·97, 95% CI 0·78–1·22; p=0·76); this finding persisted after adjustment for stratification variables (HR 1·03; 95% CI 0·81–1·29; p=0·83). Median duration of treatment with bevacizumab was 51 weeks (IQR 21–52) and dose intensity was 86% (41–96), showing good tolerability. 180 grade 3 or 4 adverse events were recorded in 101 (15%) of 671 patients in the bevacizumab group, and 36 (5%) of 672 patients in the observation group. Bevacizumab resulted in a higher incidence of grade 3 hypertension than did observation (41 [6%] vs one [ |
| وصف الملف: | application/pdf |
| تدمد: | 1470-2045 8126-1306 |
| DOI: | 10.1016/s1470-2045(14)70110-x |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c53d74344fabc0e3d30b8b3ef430dee3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c53d74344fabc0e3d30b8b3ef430dee3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14702045 81261306 |
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| DOI: | 10.1016/s1470-2045(14)70110-x |