ESMO 2018: Can Biology Help Guide Treatment Decisions in Renal Cancer?

Munich, Germany ( When assessing the completed combination trials in metastatic renal cell carcinoma (mRCC), most studies have met their anticipated endpoints. When all various treatments have been shown to be successful, this makes deciding which treatment will be right for which patients difficult.

ESMO 2018: Challenging Established Frontline Therapies in Renal Cancer

Munich, Germany ( Dr. Laurence Albiges gave a talk on the challenges faced by established frontline therapies in renal cancer. In the ESMO meeting in 2017, the Checkmate 214 trial was presented, which compared sunitinib to Nivolumab + ipilimumab in the treatment of metastatic renal cell carcinoma (mRCC) patients. This trial demonstrated a benefit in favor of the nivolumab + ipilimumab combination in poor and intermediate risk mRCC patients, with median overall survival (OS) that was not reached compared to 26 months in the sunitinib group, p<0.0001. The complete response rate (CR) was 9% vs. 1% in favor of the combination treatment.

ESMO 2018: PRINCIPAL Study - Real-World Effectiveness of Pazopanib in Patients with Intermediate Prognostic Risk Advanced Renal Cell Carcinoma

Munich, Germany ( Pazopanib is a multikinase inhibitor which limits tumor growth via inhibition of angiogenesis by inhibiting VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, FGFR-1, FGFR-3, cKIT, interleukin-2 receptor inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms)1. In a phase III trial, pazopanib was shown to be superior to placebo in both treatment naïve and cytokine-pretreated patients with advanced or metastatic RCC2.

ESMO 2018: Safety and Tolerability of Atezolizumab plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma: IMmotion 150 and IMmotion 151

Munich, Germany ( IMmotion 150 (Phase II) compared the efficacy of atezolizumab (atezo) plus bevacizumab (bev) with atezolizumab alone and sunitinib alone and then allowed for crossover in the latter 2 arms to atezolizumab plus bevacizumab1IMmotion 151  (Phase III) compared the efficacy of atezolizumab plus bevacizumab vs sunitinib for first-line therapy of metastatic renal cell carcinoma2.

ESMO 2018: KEYNOTE-427 Cohort A: Pembrolizumab Monotherapy as First-line Therapy in advanced clear cell Renal Cell Carcinoma (ccRCC)

Munich, Germany ( Several studies are underway studying PD-1/PD-L1 in combination with VEGFR or TKI blockade. Current phase III trials include pembrolizumab + axitinib, pembrolizumab + lenvatinib, avelumab + axitinib, and nivolumab + cabozantinib. Results from IMmotion 151 showed that combination therapy with atezolizumab and bevacizumab is efficacious in first-line therapy of mRCC with respect to improving progression-free survival1.

ESMO 2018: Activity of Cabozantinib After PD-1/PD-L1 Immune Checkpoint Blockade In Metastatic Clear Cell Renal Cell Carcinoma

Munich, Germany ( Cabozantinib is an oral small molecule multikinase inhibitor which targets c-MET, VEGFR2, AXL, and RET, and a standard of care therapy for both first line and second line therapy of metastatic RCC. In a phase II multicenter study which randomized patients to front-line sunitinib or cabozantinib for mRCC, cabozantinib increased median progression free survival (8.2 months vs 5.6 months) with a 34% reduction in rate of death or progression (HR 0.66, 95%CI 0.46-0.95)1.

ESMO 2018: COSMIC-021, Phase Ib Study of Cabozantinib in Combination with Atezolizumab and Potent Natural Killer, Myeloid Blood Cell Remodeling by Cabozantinib

Munich, Germany ( Cabozantinib is a multikinase inhibitor of MET, VEGFR, AXL and RET1. In the sphere of metastatic renal cell carcinoma, cabozantinib is currently being used in both first line and second line therapy, based on CABOSUN for first line and METEOR for second line2,3.  In addition to being a tyrosine kinase inhibitor, there is some evidence that cabozantinib may alter the tumor immune microenvironment, altering regulatory T cells (Tregs) as well as myeloid-derived suppressor cells (MDSC)4.
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