Continuing Education
for Urology & GU Oncology Clinicians

Conference Coverage: ESMO 2019 Kidney

Barcelona, Spain (UroToday.com)  Dr. Viktor Grunwald provided a discussion of two abstracts at the ESMO 2019 annual congress poster discussion: 911PD - A First-in-Human Phase 1/2 Trial of the Oral HIF-2a Inhibitor PT2977 in Patients with Advanced Renal Cell Carcinoma (RCC), and 912PD - Results of the Phase 2 TRAXAR Study: A Randomized Phase 2 Trial of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or metastatic (mRCC). Dr. Grunwald notes that dysregulation of the VHL-HIF axis is the basis of the anti-VEGF treatment paradigm in mRCC. So, is there a role for selective HIF inhibition in mRCC? It is important to note that there are different HIF subtype inhibitors available: HIF-1beta and HIF-2alpha. PT2385 is a HIF-2alpha inhibitor, but faced variable and unpredictable metabolism. Thus, PT2977 was developed and optimized the pharmacokinetics and is used for further clinical development.

Non-Accredited

Barcelona, Spain (UroToday.com) Endoglin is an essential angiogenic receptor expressed on proliferating tumor vessels and renal cell carcinoma (RCC) stem cells that is implicated as a mechanism of VEGF resistance. TRC105 is an endoglin monoclonal antibody that potentiates the anti-tumor activity of VEGF inhibitors in preclinical models1 and demonstrated a 29% RECIST response rate when combined with axitinib in patients with mRCC in a Phase 1b trial. At the ESMO 2019 annual congress, Dr. Toni Choueiri and colleagues presented results of the phase II TRAXAR study.

Non-Accredited

Barcelona, Spain (UroToday.com) Despite advances in clear cell renal cell carcinoma (RCC) treatment, patients with sarcomatoid RCC have a poor prognosis and are more resistant to VEGF-targeted therapy. Sarcomatoid RCC is characterized by immunologic infiltration and compared to other tumors has higher expression of PD-1 and PD-L1 on tumor infiltrating immune cells and tumor cells.1 In JAVELIN Renal 101, progression-free survival (PFS) was longer (median 13.8 vs 8.4 months; HR 0.69; p < 0.001) and objective response rate (ORR) was higher (51% vs 26%) with avelumab + axitinib versus sunitinib, and the benefit was observed in patients irrespective of PD-L1 expression and across all prognostic risk groups.2 At the ESMO 2019 annual congress, Dr. Toni Choueiri and colleagues presented results of their post hoc analysis of JAVELIN Renal 101 patients with sarcomatoid RCC.

Non-Accredited

Barcelona, Spain (UroToday.com) Inhibition of angiogenesis using either tyrosine kinase inhibitors against the VEGF receptor (e.g. pazopanib, axitinib, cabozantinib) or antibodies against circulating VEGF (e.g. bevacizumab) have been effective therapies in advanced renal cell carcinoma. Preclinical data has previously implicated endoglin, a receptor on the surface of endothelial cells, as a resistance mechanism for VEGF/VEGFR targeted therapy. Targeting endoglin with the monoclonal antibody TRC105 has been shown to potentiate VEGF/VEGFR inhibition in preclinical models. A phase 1b dose-escalation trial1 of TRC105 recently showed a 29% partial-response rate in heavily pre-treated metastatic renal cell carcinoma (mRCC) patients.

Non-Accredited

Barcelona, Spain (UroToday.com) A large-scale global survey of renal cell carcinoma (RCC) patients to capture real-world experiences has never been undertaken. The International Kidney Cancer Coalition (IKCC) is a federation of 38 affiliated patient organizations representing 1.2 million patients worldwide that is committed to reducing the global burden of kidney cancer. In this abstract, the IKCC investigators report the results of a 35-question global patient survey designed to identify geographic variations in patient education, experience and awareness, access to care, best practices, quality of life, involvement in clinical trials and to highlight unmet needs. The survey was conducted in September through October 2018 and completed online or in paper form by kidney cancer patients and/or their caregivers. The survey was distributed in 14 languages.

Non-Accredited