halo 109 301 phase iii randomized double blind placebo controlled study of pegvorhyaluronidase alfa pegph20 nab paclitaxel gemcitabine ag in patients with previously untreated hyaluronan ha high stage iv pancreatic ductal adenocarcinoma pda

n/

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

Tuber and root resistance of potato genotypes against Meloidogyne chitwoodi in the presence of Avena strigosa, related to tuber quality

Relative tuber infestation and quality of two Meloidogyne chitwoodi resistant potato genotypes, AR04-4096 and 2011M1, were compared in glasshouse experiments at initial population density (Pi) = 16 second-stage juveniles (g dry soil)−1 in the presence and absence of the bristle oat, Avena strigosa. When A. strigosa was added, Pfroot+soil (Pf= final population) on both AR04-4096 and 2011M1 increased 130×, Pftuber increased 1.9 and 3.7×, respectively, while Pftuber × fresh root weight (FRW)−1 was the same. Nematode hatch from peel of AR04-4096, without A. strigosa, was delayed by 3 weeks but relative hatching rate was increased. Although the RStuber (RS = Relative Susceptibility) of both AR04-4096 and 2011M1 were lower than 1%, in the presence of A. strigosa tuber quality of 2011M1 dropped below the marketable level, while that of AR04-4096 was hardly affected. We conclude that: i) Pftuber is influenced by root mass; ii) root quality influences nematode hatch; iii) tuber quality is not an estimator for tuber resistance, and the reverse; iv) root resistance is equal to tuber resistance

Tuber Yield, Quality and Infestation Levels of Potato Genotypes, Resistant to the Root-Knot Nematode, Meloidogyne chitwoodi

As part of developing a routine potato cultivars resistance test to Meloidogyne chitwoodi, both the effect of nematode density (Pi) and pot size on growth, tuber yield, quality and tuber infestation level were studied in glasshouse conditions. The study was carried out in four experiments using cv. Desiree as control and seven genotypes with a single resistance gene to M. chitwoodi and 1 genotype, with resistance to Globodera pallida. Plants were inoculated with ranges of Pi from 0.0625 to 256 J2 (g dry soil)−1 in log series. Haulm height, tuber yield, starch dry matter content (SDC) and tuber quality were recorded. Additionally, harvested tubers of experiment 2 were stored for 240–300 days to estimate actual tuber infestation at planting when used as seed in a subsequent season. Haulm height was positively affected with increasing Pi’s and negatively with decreasing pot size. The yield was not affected in four out of seven genotypes with resistance to M. chitwoodi; they can be considered as tolerant, having a relative minimum yield, m = 1. Three genotypes and cv. Desiree showed relative minimum yield, m 20 and are not accepted for processing. The fraction of clean tubers of the resistant genotypes had significantly increased to 91% compared to < 8% for cv. Desiree and MDG2. Tuber infestation, expressed to number of juveniles per gram dry soil of cv. Desiree after storage, showed no regression with the Pi and averaged 0.35 J2 (g dry soil)−1, while all tested genotypes provided ca. 0.002 J2 (g dry soil)−1

Targeting angiogenesis in melanoma: prospects for the future

Angiogenesis has been identified as a relevant target for melanoma experimental therapeutics, based on preclinical and clinical studies. A variety of angiogenesis inhibitors are currently being tested in both metastatic and adjuvant melanoma clinical trials. To date, the most promising evidence of benefit is based on a statistically nonsignificant trend in survival gain reported in a randomized phase II trial combining bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, with cytotoxic chemotherapy. Larger phase III studies are required to determine the true extent of clinical benefit with this class of agents. Key to these clinical trials is the need to include translational endpoints, since correlation of biological and clinical data will provide the opportunity to identify biomarkers predictive of treatment response. These biological studies will also aid our, as yet, poor understanding of the mechanism of action of angiogenesis inhibitors, as well as drug-related side effects. Finally, if these trials show meaningful clinical benefit, then careful consideration will need to be given when designing second-generation trials, in the light of novel gene-directed therapies currently showing promise in melanoma