Continuing Education
for Urology & GU Oncology Clinicians
Barcelona, Spain (UroToday.com) Hypoxia inducible factor 2α (HIF-2α) is known to mediate von Hippel-Lindau (VLH) associated oncogenesis. Deficiency of the VHL tumor suppressor leads to HIF-2α stabilization and intracellular accumulation, thereby promoting the formation of heterodimers with HIF-1β. These heterodimer acts as a key transcription factor for genes which promote tumorigenesis, such as VEGFA, thereby fueling oncogenesis.1 PT2977 (also known as MK-6482) is a small molecule inhibitor of HIF-2α which acts to block formation of the active heterodimer. Based upon promising preclinical data,2 investigators launched a clinical development program for PT2977. Eric Jonasch, MD, reported on the renal cell carcinoma dose expansion cohort of a phase I/II trial investigating the safety and efficacy of PT2977 in advanced solid tumors at ESMO 2019. A regimen of 120mg daily was selected on the basis of the dose escalation phase.
Non-Accredited
Barcelona, Spain (UroToday.com) In this session at ESMO 2019, Christian Kollmannsberger, MD, discussed the following three abstracts:
Non-Accredited
Barcelona, Spain (UroToday.com) On the basis of noninferiority outcomes for patients with metastatic disease who received sunitinib versus patients who underwent upfront cytoreductive nephrectomy followed by sunitinib,1 the role of upfront cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (RCC) who require systemic therapy has been revised. However, the activity of new combination treatments on the primary tumour is unknown. The JAVELIN Renal 101 trial demonstrated longer progression-free survival (median 13.8 vs 8.4 months; HR 0.69; p < 0.001) and higher objective response rate (51% vs 26%) with avelumab + axitinib versus sunitinib in patients with advanced RCC.2 Furthermore, benefit was observed in all risk subgroups and in patients irrespective of prior cytoreductive nephrectomy. These results led to the US FDA’s approval of the combination therapy in the first line setting for advanced RCC. Since the potential role of new combination treatments to reduce the primary tumor burden has not yet been reported, Dr. Albiges and colleagues presented results of their post hoc analysis of patients enrolled in JAVELIN Renal 101 who had not undergone upfront cytoreductive nephrectomy and had renal target lesions.
Non-Accredited
Barcelona, Spain (UroToday.com) Antiangiogenetic therapy has long been a hallmark of the treatment paradigm for metastatic renal cell carcinoma. Endoglin is an endothelial cell surface receptor that is required for angiogenesis and is highly expressed on intertumoral endothelial cells.1 TRC105 is an IgG1 class monoclonal antibody to endoglin. In preclinical models, TRC105 was capable of potentiating anti-VEGF therapy. A recently completed phase Ib trial combining TRC105 with axitinib demonstrated a promising 29% objective response rate,2 and provided the clinical rationale for the present study.
Non-Accredited
Barcelona, Spain (UroToday.com) The sarcomatoid variant is uncommon but highly aggressive histology of renal cell carcinoma which tends to exhibit worse outcomes relative to more common histologies like clear cell RCC with respect to VEGF targeted therapy. However, sarcomatoid renal cell carcinoma is also characterized by higher lymphocytic infiltration and PD-L1 expression relative to other histologies, which may lend it more responsive to checkpoint blockade immunotherapy.1
Non-Accredited