Results of bevacizumab biosimilar compared with RMP for the treatment of metastatic colorectal cancer.

e14065 Background: BEVZ92 has being developed as a proposed biosimilar approved reference medicine product (RMP). BEVZ92 has an identical amino acid sequence and highly similar physicochemical and in vitro functional properties to RMP. The aim of this study was to demonstrate pharmacokinetics (PK) similarity of BEVZ92 to RMP, in combination in combination with FOLFOX or FOLFIRI, as first-line treatment in patients with mCRC (NCT02069704). Methods: PK analysis for multiple dose studies was conducted, as per guidelines, measuring the total exposure area under the concentration-time profile (AUC0-336) at cycle 1, and to the end of the dosing interval at steady-state (AUCss) at cycle 7. PK similarity was achieved if 90% confidence interval (CI) for the test-to-reference ratios of AUC0-336h and AUCss were within 80.00–125.00% bioequivalence acceptance window. Secondary endpoints included other PK parameters, safety profile, immunogenicity and objective response rate (ORR). Results: A total of 142 patients were randomized and treated. Bevacizumab serum concentrations showed a ratio (90% CI) of geometric means for BEVZ92 and RMP were 99.4% (90.5%-109%) and 100% (90.2%–112%) for AUC0-336h and AUCss, respectively. All secondary PK endpoints which include Cmax, Ctrough, Tmax, t1/2, Kel, CL, Vd, and RA-AUC were also similar between the two arms. The ORR was 45% (95% CI, 33% to 57%) for BEVZ92, and 52% (95% CI, 40% to 64%) for RMP. Immunogenicity results showed a low incidence in the anti-drug antibodies de novo development and similar between both arms. Safety profile in terms of nature, frequency and severity was similar to the RMP and according to what is expected given the underlying disease and concurrent use of chemotherapy. Conclusions: These study results confirm the bioequivalence of BEVZ92 and the RMP in a real and common clinical setting, and translates the high similarity demonstrated in the in vitro and in vivo characterization into the clinical outcomes such as efficacy, immunogenicity and safety profile. Clinical trial information: NCT02069704.

ACCEPTANCE DEPENDENCE OF FLUCTUATION IN PARTICLE MULTIPLICITY

The effect of limiting the acceptance in rapidity on event-by-event multiplicity fluctuations in nucleus–nucleus collisions has been investigated. Our analysis shows that the multiplicity fluctuations decrease when the rapidity acceptance is decreased. We explain this trend by assuming that the probability distribution of the particles in the smaller acceptance window follows binomial distribution. Following a simple statistical analysis, we conclude that the event-by-event multiplicity fluctuations for full acceptance are likely to be larger than those observed in the experiments, since the experiments usually have detectors with limited acceptance. We discuss the application of our model to simulated data generated using VENUS, a widely used event generator in heavy-ion collisions. We also discuss the results from our calculations in the presence of dynamical fluctuations and possible observation of these in the actual data.

The Effects of Collimation on PET Image Noise Due to Scatter, Random Counts, and Deadtime

The rates for true coincident events, scattered events, and singles in a Positron Emission Tomograph (PET) depend on the collimator size and shape. Monte Carlo techniques were used to compare efficiencies for wanted and unwanted events in multislice PET (MS-PET) and open collimator positron volumetric imaging (PVI) configurations. All systems used cylindrical arrays of bismuth germanate (BGO) or NaI crystals 51 cm in diameter and 10 cm deep suitable for whole brain imaging. The PVI systems detect about five times more true coincident events at low activity concentrations, but their scatter fraction is about three times higher. They are also much more sensitive to activity outside the scan field. As well as causing random counts when they fall within the energy acceptance window, single events are the main cause of deadtime. When the detectors are made from light-encoded blocks deadtime is the major limitation at high count rates. When discrete crystals are used, the efficiency is lower and the random count rates are a more significant source of noise. Noise-effective count rates are used to compare the relative cost in system performance among different systems and sources of noise.