Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial

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

State of the world’s plants and fungi 2020

Kew’s State of the World’s Plants and Fungi project provides assessments of our current knowledge of the diversity of plants and fungi on Earth, the global threats that they face, and the policies to safeguard them. Produced in conjunction with an international scientific symposium, Kew’s State of the World’s Plants and Fungi sets an important international standard from which we can annually track trends in the global status of plant and fungal diversity

A vector expressing feline mature IL-18 fused to IL-1 beta antagonist protein signal sequence is an effective adjuvant to a DNA vaccine for feline leukaemia virus

DNA vaccination using vectors expressing the gag/pol and env genes of feline leukaemia virus (FeLV) and plasmids encoding feline interleukin-12 (IL-12) and IL-18 completely protected cats from viraemia following challenge [Hanlon L, Argyle D, Bain D, Nicolson L, Dunham S, Golder MC, et al. Feline leukaemia virus DNA vaccine efficacy is enhanced by coadministration with interleukin-12 (IL-12) and IL-18 expression vectors. J Virol 2001;75:8424–33]. However, the relative contribution of each cytokine gene towards protection is unknown. This study aimed to resolve this issue. IL-12 and IL-18 constructs were modified to ensure effective expression, and bioactivity was demonstrated using specific assays. Kittens were immunised intramuscularly with FeLV DNA and various cytokine constructs. Together with control kittens, these were challenged oronasally with FeLV and monitored for 15 weeks. All six kittens given FeLV, IL-12 and IL-18 were protected from the establishment of persistent viraemia and four from latent infection. Of six kittens immunised with FeLV DNA and IL-18, all were protected from viraemia and five from latent infection. In contrast, three of five kittens given FeLV DNA and IL-12 became persistently viraemic. Therefore, the adjuvant effect on the FeLV DNA vaccine appears to reside in the expression of IL-18