Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.
MetadataShow full item record
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.
Version of record
Neoplasm Recurrence, Local
Proto-Oncogene Proteins B-raf
Drug Administration Schedule
Aged, 80 and over
Dermatologic Surgical Procedures
License start date
Annals of oncology : official journal of the European Society for Medical Oncology, 2018, 29 (8), pp. 1843 - 1852
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Showing items related by title, author, creator and subject.
Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma. Bridgeman, VL; Wan, E; Foo, S; Nathan, MR; Welti, JC; Frentzas, S; Vermeulen, PB; Preece, N; Springer, CJ; Powles, T; Nathan, PD; Larkin, J; Gore, M; Vasudev, NS; Reynolds, AR (2016-01)Sunitinib and pazopanib are antiangiogenic tyrosine kinase inhibitors (TKI) used to treat metastatic renal cell carcinoma (RCC). However, the ability of these drugs to extend progression-free and overall survival in this ...
Safety and Treatment Outcomes of Nivolumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Retrospective Multicenter Cohort Study. Vasiliadou, I; Breik, O; Baker, H; Leslie, I; Sim, VR; Hegarty, G; Michaelidou, A; Nathan, K; Hartley, A; Good, J; Sanghera, P; Fong, C; Urbano, TG; Lei, M; Petkar, I; Ferreira, MR; Nutting, C; Wong, KH; Newbold, K; Harrington, K; Bhide, S; Kong, A (2021-03-19)Nivolumab is an anti-PD-1 monoclonal antibody currently used as immunotherapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with evidence of disease progression after platinum-based ...
The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures Al-Buheissi, SZ; Cole, KJ; Hewer, A; Kumar, V; Bryan, RL; Hudson, DL; Patel, HR; Nathan, S; Miller, RA; Phillips, DH (WILEY-BLACKWELL, 2006-06-01)BACKGROUND. Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT). METHODS. We investigated by Western blotting ...