Research Spotlight

Posted April 15th 2018

Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study.

Thomas Hutson D.O.

Thomas Hutson D.O.

Molina, A. M., T. E. Hutson, D. Nosov, P. Tomczak, O. Lipatov, C. N. Sternberg, R. Motzer and T. Eisen (2018). “Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study.” Eur J Cancer 94: 87-94.

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BACKGROUND: Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 tyrosine kinases. This open-label, crossover clinical study (AV-951-09-902) provided access to tivozanib for patients who progressed on sorafenib in TIVO-1, comparing tivozanib with sorafenib in patients with advanced renal cell carcinoma (RCC). METHODS: Patients enrolled in this single-arm, phase 2 crossover study were previously randomised to sorafenib on TIVO-1, progressed and then crossed over to tivozanib. Patients received tivozanib (1.5 mg/day orally; 3 weeks on/1 week off) within 4 weeks after their last sorafenib dose. FINDINGS: Crossover patients were exposed to tivozanib for a median of eight cycles. From the start of tivozanib treatment, median progression-free survival was 11.0 months (95% confidence interval [CI]: 7.3-12.7) and median overall survival was 21.6 months (95% CI: 17.0-27.6). Best overall response was partial response in 29 (18%) patients and stable disease in 83 (52%) patients, with a median duration of response of 15.2 and 12.7 months, respectively. About 77% of patients experienced adverse events, most frequently hypertension (26%), followed by diarrhoea (14%) and fatigue (13%); 53% of patients had treatment-related adverse events, including 24% grade >/=3. About 9% and 16% of patients had dose reductions and dose interruptions due to adverse events, respectively. A total of 30% of patients had serious adverse events, and 4% had treatment-related serious adverse events. INTERPRETATION: This crossover study of patients with advanced RCC demonstrated potent tivozanib anti-tumour activity. Safety and tolerability profiles were acceptable and consistent with the established adverse event profile of tivozanib.


Posted April 15th 2018

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

Ajay Goel Ph.D.

Ajay Goel Ph.D.

Mohapatra, S. S., S. K. Batra, S. Bharadwaj, M. Bouvet, B. Cosman, A. Goel, W. Jogunoori, M. J. Kelley, L. Mishra, B. Mishra, S. Mohapatra, B. Patel, J. R. Pisegna, J. P. Raufman, S. Rao, H. Roy, M. Scheuner, S. Singh, G. Vidyarthi and J. White (2018). “Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.” Dig Dis Sci. 63(5): 1123-1138. Epub March 25.

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Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA’s research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.


Posted April 15th 2018

Prevalence of genital psoriasis in patients with psoriasis.

Alan M. Menter M.D.

Alan M. Menter M.D.

Meeuwis, K. A. P., A. Potts Bleakman, P. C. M. van de Kerkhof, Y. Dutronc, C. Henneges, L. J. Kornberg and A. Menter (2018). “Prevalence of genital psoriasis in patients with psoriasis.” J Dermatolog Treat Mar 28. [Epub ahead of print].

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BACKGROUND: Psoriatic lesions in the genital area (GenPs) can cause considerable physical and emotional distress. To increase physician awareness, we estimated the GenPs prevalence among patients with psoriasis. METHODS: An English language literature search was performed. Articles reporting GenPs prevalence met the search criteria and were included. Because GenPs is rarely reported in demographics of prospective clinical trials, GenPs prevalence and baseline demographics of patients with and without GenPs in two prospective randomized phase 3b trials (NCT02561806 and NCT02634801) involving patients with moderate-to-severe psoriasis are reported. RESULTS: Overall, 600 references were screened. Eighteen articles met the search criteria. Patient populations were highly heterogeneous across articles. Broadly, the presence of GenPs was either physician-reported (physical examinations) or patient-reported (questionnaires). In the literature, GenPs prevalence at the time of reporting ranged from 7% to 42% and the prevalence of GenPs at any time during the course of psoriasis ranged from 33% to 63%. In the two prospective clinical trials, the prevalence of GenPs at the time of enrollment was 35-42%. CONCLUSION: A substantial proportion of patients experience genital lesions at some time during the course of psoriasis. Increased awareness of GenPs prevalence may drive improved assessment and treatment.


Posted April 15th 2018

Interpreting the Wide Range of NT-proBNP Concentrations in Clinical Decision Making./h3>

Peter McCullough M.D.

Peter McCullough M.D.

McCullough, P. A. and A. Y. Kluger (2018). “Interpreting the Wide Range of NT-proBNP Concentrations in Clinical Decision Making.” J Am Coll Cardiol 71(11): 1201-1203.

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NT-proBNP is a contextual test and must be interpreted in terms of the indication (diagnostic or prognostic aid), age, renal function, and other factors. ICON-RELOADED has moved the field forward with important prospective, blinded, and adjudicated data demonstrating the utility of NT-proBNP in the real-world setting; however, it has also reloaded interpretative caveats for the clinician and demonstrated that no single cutpoint can be applied in clinical practice. (Excerpt from text, p. 1202; no abstract available.)


Posted April 15th 2018

Iso-osmolar contrast media and adverse renal and cardiac events after percutaneous cardiovascular intervention.

Peter McCullough M.D.

Peter McCullough M.D.

McCullough, P. A., G. David, T. M. Todoran, E. S. Brilakis, M. P. Ryan and C. Gunnarsson (2018). “Iso-osmolar contrast media and adverse renal and cardiac events after percutaneous cardiovascular intervention.” J Comp Eff Res 7(4): 331-341.

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AIM: To assess the relationship between type of contrast media (CM), iso-osmolar contrast media (IOCM) or low-osmolar contrast media (LOCM), and major adverse renal and cardiovascular events (MARCE). MATERIALS & METHODS: Coronary or peripheral angioplasty visits were stratified into CM cohorts: IOCM or LOCM. Multivariable regression analysis used hospital fixed effects to assess the relationship between MARCE events and type of CM. RESULTS: Among 333,533 visits (357 hospitals), the incidence of MARCE was 7.41%. After controlling for observable and unobservable time invariant within-hospital characteristics, administration of IOCM versus LOCM was associated with a 0.69% absolute and 9.32% relative risk reduction in MARCE rate. CONCLUSION: Our study indicates that as compared with LOCM, IOCM may be associated with reduction of MARCE events in coronary or peripheral angioplasty patients.