The results of crossbreeding between chios and the local fat-tail awassi

International audienc

The impact of COVID-19 on cancer care and oncology clinical research: an experts’ perspective

COVID-19; Cancer care; Clinical researchCOVID-19; Cura del càncer; Recerca clínicaCOVID-19; Cuidado del cancer; Investigación clínicaThe coronavirus disease-19 (COVID-19) pandemic promises to have lasting impacts on cancer clinical trials that could lead to faster patient access to new treatments. In this article, an international panel of oncology experts discusses the lasting impacts of the pandemic on oncology clinical trials and proposes solutions for clinical trial stakeholders, with the support of recent data on worldwide clinical trials collected by IQVIA. These lasting impacts and proposed solutions encompass three topic areas. Firstly, acceleration and implementation of new operational approaches to oncology trials with patient-centric, fully decentralized virtual approaches that include remote assessments via telemedicine and remote devices. Geographical differences in the uptake of remote technology, including telemedicine, are discussed in the article, focusing on the impact of the local adoption of new operational approaches. Secondly, innovative clinical trials. The pandemic has highlighted the need for new trial designs that accelerate research and limit risks and burden for patients while driving optimization of clinical trial objectives and endpoints, while testing is being minimized. Areas of considerations for clinical trial stakeholders are discussed in detail. In addition, the COVID-19 pandemic has exposed the underrepresentation of minority groups in clinical trials; the approach for oncology clinical trials to improve generalizability of efficacy and outcomes data is discussed. Thirdly, a new problem-focused collaborative framework between oncology trial stakeholders, including decision makers, to leverage and further accelerate the innovative approaches in clinical research developed during the COVID-19 pandemic. This could shorten timelines for patient access to new treatments by addressing the cultural and technological barriers to adopting new operational approaches and innovative clinical trials. The role of the different stakeholders is described, with the aim of making COVID-19 a catalyst for positive change in oncology clinical research and eventually in cancer care

The impact of prior platinum therapy on survival in patients with metastatic urothelial cancer receiving vinflunine

Background: A phase III trial demonstrated an overall survival advantage with the addition of vinflunine to best supportive care (BSC) in platinum-refractory advanced urothelial cancer. We subsequently examined the impact of an additional 2 years of survival follow-up and evaluated the influence of first-line platinum therapy on survival. Methods: The 357 eligible patients from the phase III study were categorised into two cohorts depending on prior cisplatin treatment: cisplatin or non-cisplatin. Survival was calculated using the Kaplan–Meier method. Results: The majority had received prior cisplatin (70.3%). Survival was higher in the cisplatin group (HR: 0.76; CI 95% 0.58–0.99; P=0.04) irrespective of treatment arm. Multivariate analysis including known prognostic factors (liver involvement, haemoglobin, performance status) and prior platinum administration did not show an independent effect of cisplatin. Vinflunine reduced the risk of death by 24% in the cisplatin-group (HR: 0.76; CI 95% 0.58–0.99; P=0.04) and by 35% in non-cisplatin patients (HR: 0.65; CI 95% 0.41–1.04; P=0.07). Interpretation: Differences in prognostic factors between patients who can receive prior cisplatin and those who cannot may explain the survival differences in patients who undergo second line therapy. Prior cisplatin administration did not diminish the subsequent benefit of vinflunine over BSC

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436

The potential direct economic impact and private management costs of an invasive alien species:Xylella fastidiosa on Lebanese wine grapes

Since its outbreak in 2013 in Italy, the harmful bacterium Xylella fastidiosa has continued to spread through-out the Euro-Mediterranean basin and, more recently, in the Middle East region. Xylella fastidiosa subsp. fastidiosa is the causal agent of Pierce’s disease on grapevines. At present, this alien subspecies has not been reported in Lebanon but if this biological invader was to spread with no cost-effective and sustainable management, it would put Lebanese vineyards at a certain level of risk. In the absence of an Xylella fastidiosa subsp. fastidiosa outbreak, the gross revenue generated by Lebanese wine growers is estimated as close to US$22 million/year for an average period of 5 years (2015–2019). The potential quantitative economic impacts of an Xylella fastidiosa subsp. fastidiosa outbreak and particularly, the private control costs have not been assessed yet for this country as well as for others which Xylella fastidiosa may invade. Here, we have aimed to estimate the potential direct economic impact on growers’ livelihoods and provide the first estimate of the private management costs that a theoretical Xylella fastidiosa subsp. fastidiosa outbreak in Lebanon would involve. For this purpose, we used a Partial Budget approach at the farm gate. For the country as a whole, we estimated that a hypothetical full spread of Xylella fastidiosa subsp. fastidiosa on Lebanese wine grapes would lead to maximum potential gross revenue losses of almost US$ 11 million for an average recovery period of4 years, to around US$82.44 million for an average grapevine life span period of 30 years in which infected plants are not replaced at all. The first yearly estimated additional management cost is US$853 per potentially infected hectare. For a recovery period of 4 years, the aggregate estimated additional cost would reach US$2374/ha, while the aggregate net change in profit would be US$-4046/ha. Furthermore, additional work will be needed to estimate the public costs of an Xylella fastidiosa subsp. fastidiosa outbreak in Lebanon. The observed costs in this study support the concerned policy makers and stakeholders to implement a set of reduction management options against Xylella fastidiosa subsp. fastidiosa at both national and wine growers’ levels. This re-emerging alien biota should not be neglected in this country. This understanding of thepotential direct economic impact of Xylella fastidiosa subsp. fastidiosa and the private management costs can also benefit further larger-scale studies covering other potential infection areas and plant hosts

Colloidal analogs of molecular chain stoppers

Self-assembly of nanoparticles in polymer-like chains bears a strong similarity to polymerization reactions, in which monomer units are brought together by directional noncovalent interactions. Based on this similarity, the molecular concepts of polymer chemistry can be applied to achieve controllable nanoparticle assembly. On the other hand, the ability to visualize nanoparticle assemblies and to exploit characterization tools used in nanoscience offers a unique way to study polymerization reactions. Here we explore this twofold strategy for an exemplary system including the self-assembly of bifunctional metal nanorods in the presence of monofunctional nanoparticles (chain stoppers). The approach provided insight into the polymerization kinetics, side reactions, the distribution of species in the system, and the design rules for the synthesis of molecular chain stoppers

COMPARZ Post Hoc Analysis: Characterizing Pazopanib Responders With Advanced Renal Cell Carcinoma

Background: The phase III COMPARZ study showed noninferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma. In this COMPARZ post hoc analysis we characterized pazopanib responders, patient subgroups with better outcomes, and the effect of dose modification on efficacy and safety. Patients and Methods: Patients were randomized to pazopanib 800 mg/d (n = 557) or sunitinib 50 mg/d, 4 weeks on/2 weeks off (n = 553). Secondary end points included time to complete response (CR)/partial response (PR); the proportion of patients with CR/PR ≥10 months and progression-free survival (PFS) ≥10 months; efficacy in patients with baseline metastasis; and logistic regression analyses of patient characteristics associated with CR/PR ≥10 months. Median PFS, objective response rate (ORR), and safety were evaluated in patients with or without dose reductions or interruptions lasting ≥7 days. Results: Median time to response was numerically shorter for patients treated with pazopanib versus sunitinib (11.9 vs. 17.4 weeks). Similar percentages of pazopanib and sunitinib patients had CR/PR ≥10 months (14% and 13%, respectively), and PFS ≥10 months (31% and 34%, respectively). For patients without versus with adverse event (AE)-related dose reductions, median PFS, median overall survival, and ORR were 7.3 versus 12.5 months, 21.7 versus 36.8 months, and 22% versus 42% (all P <.0001) for pazopanib, and 5.5 versus 13.8 months, 18.1 versus 38.0 months, and 16% versus 34% (all P <.0001) for sunitinib; results were similar for dose interruptions. Conclusion: Dose modifications when required because of AEs were associated with improved efficacy, suggesting that AEs might be used as a surrogate marker of adequate dosing for individual patients

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

This randomised phase III trial compared standard of care Everolimus with the anti-PD1 monoclonal antibody Nivolumab in previously treated patients with locally advanced inoperable or metastatic clear cell renal cancer. 810 patients were randomised to receive either Everolimus 10 mg orally daily or 3 mg/kg of Nivolumab intravenously every two weeks. Patients were treated until unacceptable toxicity or disease progression. Patients could be treated beyond progression if the investigator believed that the patient was gaining clinical benefit. The primary endpoint was overall survival. The median survival was 25 months for Nivolumab and 19.8 months for Everolimus (p=0.002). The objective response rate was higher for Nivolumab (25 versus 5%; p=<0.001).The median progression free survivals were 4.6 & 4.4 months (p=0.11). Grade 3 & 4 treatment related toxicities were observed in 19 & 37% of patients on Nivolumab or Everolimus respectively. In patients with previously treated renal cell carcinoma Nivolumab produced superior survival and more tolerable treatment than Everolimus

Costo-Efficacia di cabozantinib nel trattamento di seconda linea del tumore a cellule renali metastatico (mRCC) in Italia:

Introduction: Renal cell carcinoma (RCC) is the most common form of kidney cancer with >30% already metastatic at diagnosis. For patients who fail tyrosine kinase inhibitor (TKI) therapy, the Italian Medical Oncology Association recommends (level IA) nivolumab and cabozantinib. The aim of this study was to compare the cost-effectiveness of cabozantinib with nivolumab for treatment of adult patients with mRCC following prior TKI therapy in Italy. Methods: A partitioned survival (area under the curve) model was developed for the Italian medical environment. Cost-effectiveness was assessed from the Italian National Healthcare Service (SSN) perspective over a 30-year time horizon (annual discount: 3% rate). In the absence of head-to-head studies, clinical evidence was based on results of network meta-analysis. Health-state-related utilities were informed by EQ-5D data from the METEOR study. Resource use and costs were obtained from published sources. Results: Treatment with cabozantinib dominates nivolumab across a 30-years time horizon. In the reference case, treatment with cabozantinib results in an incremental 0.268 quality-adjusted life years (QALY) and an incremental 0.349 life years (LY) gained with a total saving, for the Italian SSN, of €5,605 compared to nivolumab over 30 years. Cabozantinib is associated with gains in quality adjusted life years versus nivolumab, in all analyses. Results were shown to be sensitive to drug prices variation and robust when altering other parameters. Discussion: Cabozantinib represents an efficient option in the management of mRCC after initial TKI-therapy in Italy. Drug prices impact final results, and this must be carefully considered, especially considering the confidential discounts and outcome/financial-based agreements currently in place in Italy