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Kidney knowledge base featuring commentary on clinical trials.
Commentaries from Professor Susanne Osanto on current clinical trials within Renal Cell Carcinoma
Updates to these commentaries and further trials will be commented on over the coming months.
Latest update 10th April 2014
Since 2005 we witnessed an unprecedented progress in the treatment of advanced RCC. Several targeted therapies have become available for first- and second-line use including sorafenib, sunitinib, bevacizumab (plus IFN-α), temsirolimus, everolimus, pazopanib, and, most recently, axitinib. The currently approved drugs, most of which are oral compounds, are given continuously but treatment resistance will occur eventually. Developing a better understanding of primary and acquired mechanisms of resistance and feedback responses are critical for rational drug and combination therapy development. Most of the targeted therapies to date provide only temporary responses due to emergence of resistance. For that reason, combination strategies were anticipated to more likely have better outcomes. But thus far, combination strategies have failed in RCC.
As there are no new other classes of drugs registered (yet) for the treatment of advanced RCC, remaining open questions with regard to superiority or non-inferiority of single agents or combinations in first-line or second-line have been addressed in the latest trials presented in the second half of 2013 and in 2014. Another relevant question was the best sequence to use currently available drugs.
In mRCC trials, progression-free survival (PFS) has been used as primary endpoint and PFS served as the basis of approval for several targeted therapies. However, as overall survival data are emerging from more recent trials, whether the optimal sequence of first-line, second-line and third-line choices in relation to costs and quality of life (toxicity of compounds and co-morbidity of the patients) becomes very important.
Thus, ongoing and future challenges include the investigation of rational ways to sequence or combine current and new agents. But most importantly, there is an unmet need for novel classes of effective agents.
Kidney Cancer News from ASCO 2014
Commentaries from Susanne Osanto on a selection of presentations within Kidney Cancer from this year’s ASCO meeting.
Schoots IG, Zaccai K, Hunink MG, Verhagen PCMS.J Urol. 2017 Jul;198(1):12-21.
Editorial comment from Piotr Chlosta:
In a systematic review evaluating Bosniak classification system for complex renal cysts, the authors conclude that its effectiveness was high for categories II, IIF and IV, whereas low for category III. In category III, surgical overtreatment rate was 49% because of benign pathology. This, together with good oncological outcomes of Bosniak III cysts might suggest that surveillance could be an alternative approach for consideration in this group, warranting further studies to assess safety of surveillance strategy.
Cryoablation versus Partial Nephrectomy for Clinical T1b Renal Tumors: A Matched Group Comparative Analysis
Peter A. Caputo, Homayoun Zargar, Daniel Ramirez, Hiury S. Andrade, Oktay Akca, Tianming Gao, Jihad H. Kaouk
European Urology, Volume 71, Issue 1, January 2017, Pages 111 - 117
Editorial comment from Piotr Chlosta: Patients treated with cryoablation(CA) for cT1b renal tumors had a significantly higher rate of local cancer recurrence at 1 year compared to those treated with partial nephrectomy (PN). The authors found a higher but not significantly different postoperative complication rate for the PN group, a significantly higher local recurrence rate for the CA group, and similar overall and cancer-specific survival. The role of CA for cT1b RCC need to be determined.
Adjuvant Treatment for High-Risk Clear Cell Renal Cancer: Updated Results of a High-Risk Subset of the ASSURE Randomized Trial
Haas NB, Manola J, Dutcher JP, Flaherty KT, Uzzo RG, Atkins MB, et al.JAMA Oncol. 2017 Mar 9. [Epub ahead of print]
Editorial comment from Piotr Chlosta: Analysis of data from ASSURE trial showed that adjuvant treatment with sunitinib or sorafenib did not improve disease-free survival in high-risk subset of patients with clear cell RCC.
Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors
L. Derosa, B. Routy, D. Enot, G. Baciarello, C. Massard, Y. Loriot, et al.J Clin Oncol 35, 2017 (Suppl 6S; abstract 462)
Editorial comment from Prof. Piotr Chlosta:
This retrospective analysis suggests efficacy of immunotherapy may be lower in patients receiving antibiotic less than a month before starting treatment. Relationship between the gut microbiome and response to immunotherapy should be further investigated.
European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor–Targeted Therapy
Thomas Powles, Michael Staehler, Börje Ljungberg, Karim Bensalah, Steven E. Canfield, Saeed Dabestani, Rachel H. Giles, Fabian Hofmann, Milan Hora, Markus A. Kuczyk, Thomas Lam, Lorenzo Marconi, Axel S. Merseburger, Alessandro Volpe, Axel Bex
Editorial comment from Piotr Chlosta:
Following publication of data from pivotal trials, the European Association of Urology renal cancer guidelines panel recommends nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of VEGF-targeted therapy.
Outcomes Following Complete Surgical Metastasectomy for Patients with Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis
Zaid HB, Parker WP, Safdar NS, Gershman B, Erwin PJ, Murad MH, et al.J Urol. 2017 Jan;197(1):44-49
Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC)
BJU Int. 2014 Oct;114(Suppl 4):2Abstract Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has clinical activity in mRCC. VEGF TKIs suppress regulatory...
Characterizing the Impact of Lymph Node Metastases on the Survival Outcome for Metastatic Renal Cell Carcinoma Patients Treated with Targeted Therapies
Nils Kroeger, Allan J. Pantuck, J. Connor Wells, Nicola Lawrence, Reuben Broom, Jenny J. Kim, Sandy Srinivas, Jessica Yim, Georg A. Bjarnason, Arnoud Templeton, Jennifer Knox, Ezra Bernstein, Martin Smoragiewicz, Jae Lee, Brian I. Rini, Ulka N. Vaishampayan, Lori A. Wood, Benoit Beuselinck, Frede Donskov, Toni K. Choueiri, Daniel Y. Heng
European Urology, Volume 68, Issue 3, September 2015, Pages 506 - 515
Clinical and radiographic predictors of the need for resection of the inferior vena cava during nephrectomy for patients with renal cell carcinoma and caval tumor thrombus
BJU Int. 2014 Oct;114(Suppl 4):14-15.BJU Int. 2014 Oct;114(Suppl 4):14-15. Abstract Objective: To evaluate clinical and radiographic predictors of need for resection of the inferior...
Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium
Christos E. Kyriakopoulos, Namita Chittoria, Toni K. Choueiri, Nils Kroeger, Jae-Lyun Lee, Sandy Srinivas, Jennifer J. Knox, Georg A. Bjarnason, Scott D. Ernst, Lori A. Wood, Ulka N. Vaishampayan, Neeraj Agarwal, Sumanta K. Pal, Ravindran Kanesvaran, Sun-Young Rha, Takeshi Yuasa, Frede Donskov, Scott A. North, Daniel Y. Heng, Brian I. Rini
Clinical Genitourinary Cancer, 2, 13, pages e79 - e85
EAU 2017 Scientific Programme and Sessions
View the Scientific Programme and Sessions of the 2017 EAU Annual Congress, Munich, Germany.