Continuing Education
for Urology & GU Oncology Clinicians

Conference Coverage: ESMO 2019 Kidney

Barcelona, Spain (UroToday.com) To date, there have been no robust predictors of response to nivolumab for patients with metastatic renal cell carcinoma (mRCC). Previously, the NIVOREN GETUG-AFU 26 study reported safety and efficacy of nivolumab in clear cell mRCC patients in a “real world setting”, noting a response rate of 21%, median PFS of 3.7 months and median OS of 24.5 months.1 Thereafter, a translational research program was launched to characterize immune cell populations in and around the tumor by immunohistochemistry (IHC) and correlate them with outcome on nivolumab treatment. At the ESMO 2019 annual congress, Dr. Vano and colleagues presented the initial results of their translational work. 

Non-Accredited

Barcelona, Spain (UroToday.com) The Von Hippel Lindau – Hypoxia Inducible Factor signaling axis is dysregulated in renal cell carcinoma. PT2977 is a small molecular inhibitor of HIF-2alpha, a key oncogenic driver within the VHL-HIF signaling pathway. Pre-clinical data indicates that this inhibitor blocks the association of HIF-2alpha with HIF-1beta, thus blocking the expression of genes important for cell growth and inhibiting the growth of mouse models of renal cell carcinoma.

Non-Accredited

Barcelona, Spain (UroToday.com) Sarcomatoid differentiation can occur in all subtypes of renal cell carcinoma (RCC) and is associated with an aggressive phenotype. Sarcomatoid RCC (sRCC) is characterized by immunologic infiltration and has with higher PD-1/PD-L1 on tumor cells and tumor-infiltrating immune cells. JAVELIN Renal 101 demonstrated a significant improvement in progression-free survival (PFS) with avelumab plus axitinib (A + Ax) versus sunitinib (median PFS 13.8 vs 8.4 months, HR 0.69, p < 0.001) in patients with previously untreated clear cell mRCC.1 This abstract reports the efficacy and biomarker results from a post-hoc analysis of patients enrolled in JAVELIN Renal 101 who had sarcomatoid features in their tumor histology.

Non-Accredited

Barcelona, Spain (UroToday.com) Overall, 16% of all patients diagnosed with renal cell carcinoma (RCC) have loco-regional disease at diagnosis, and 40% of these patients relapse after a radical nephrectomy with metastasis. In the S-TRAC trial, adjuvant sunitinib prolonged disease-free survival (DFS) versus placebo in patients with loco-regional RCC at high risk of recurrence after nephrectomy (HR 0.76, 95% CI 0.59-0.98, p = 0.03).1 Subsequently, Ravaud et al. previously applied the 16-gene Recurrence Score and confirmed its prognostic value.2 At the ESMO 2019 poster discussion, Dr. Ravaud and colleagues reported the results of their retrospective exploratory genomic and transcriptomic analyses using nephrectomy biospecimens from the S-TRAC trial.

Non-Accredited

Barcelona, Spain (UroToday.com) Hypoxia-inducible factor (HIF)-2α is a transcription factor that is a key oncogenic driver in renal cell carcinoma (RCC) attributed, in 80-90% of patients, to the underlying protein product of von Hippel-Lindau tumor suppressor gene deficiency.1VHL gene inactivation leads to accumulation of HIF-2α, which heterodimerizes with HIF-1β and activates the transcription of genes associated with tumor progression, such as VEGFA, CCND1, CXCR4, and TGFA2.1 PT2977 is a potent and selective small molecule HIF-2α inhibitor that prevents HIF-2α from heterodimerizing with HIF-1β, blocking the expression of HIF-2α target genes in tumour cells, and inducing regressions in mouse xenograft RCC models. The objective of the current study was to evaluate the efficacy and safety of PT2977 (MK-6482) for the treatment of advanced clear cell RCC, presented at ESMO 2019 by Dr. Eric Jonasch and colleagues.

Non-Accredited