Immune Checkpoint Inhibition, the Key to Success in Renal Cell Carcinoma?

Treatment of renal cell carcinoma (RCC) has evolved rapidly since the development of checkpoint inhibitors. Most of the studies have been conducted in patients with metastatic disease and led to a significant change in the treatment landscape. Currently, many studies are investigating immune checkpoint inhibition (ICI) in the neoadjuvant and adjuvant setting and the efficacy of combination therapies. It remains difficult to predict which patients will respond best. Consequently, there is a high need for predictive biomarkers. In this review, we discuss the different studies with ICI in RCC and the molecular correlates with clinical outcome.

Individualization of Dose and Schedule Based On Toxicity for Oral VEGF Drugs in Kidney Cancer

The introduction of oral vascular endothelial growth factor receptor tyrosine kinase inhibitors therapy has been associated with major improvements in outcome for patients with metastatic kidney cancer. Each drug has been licensed with rigid dosing criteria that are not optimal for all patients. This paper reviews the growing body of evidence suggesting that individualized dosing based on toxicity may be associated with optimal drug exposure for each patient and improved outcome both in the metastatic and adjuvant setting.

The Value of Multiparametric MRI for Assessment of Inferior Vena Cava Wall Invasion by Renal Cell Carcinoma Thrombus: A Prospective Feasibility Study

Background: Renal cell carcinoma (RCC) thrombus invasion in the inferior vena cava (IVC) wall needs adequate resection to improve survival. Surgical planning to avoid positive vascular surgical margins and recurrent disease can be facilitated by imaging capable of diagnosing this invasion and the extent of the thrombus. Objective: To evaluate the diagnostic performance of multiparametric MR imaging (mpMRI) for detecting inferior vena cava (IVC) wall invasion and extent of renal cell carcinoma (RCC) thrombus. Methods: In this prospective study, twenty consecutive patients underwent mpMRI before open radical nephrectomy with IVC thrombectomy was performed in a single 

Real-World Results from One Year of Therapy with Tivozanib

We report our one-year experience on the use of Tivozanib in metastatic Renal Cell Carcinoma (RCC) in n=23 patients treated within a year after approval. Tumor response according to RECIST criteria was PR in 39.1%, SD in 52.2% and PD in 8.7% of the patients. Median progression free survival (PFS) was 14.9 months (95% CI 5.1-24.8).

Utility of FDG-PET/CT in Patients with Advanced Renal Cell Carcinoma with Osseous Metastases: Comparison with CT and 99mTc-MDP Bone Scan in a Prospective Clinical Trial

Objective: Compare FDG-PET/CT, CT, and bone scan for detecting and monitoring bone metastases’ response in metastatic renal cell cancer (mRCC). Methods: Patients with mRCC prospectively underwent FDG-PET/CT, CT, and bone scans at baseline and after 8 weeks of therapy. Tumor visibility and metabolic activity were retrospectively recorded. Response was evaluated by PERCIST, RECIST, and MD Anderson bone criteria. Kaplan-Meier methodology estimated event-time distributions for PFS, OS, and time to symptomatic skeletal event (SSE). Log-rank test tested differences in event-time distributions between response at 8 weeks by response criteria. Results: Sixteen patients (n  = 30; 53%) were evaluable. 

Predictors of Survival Outcomes in Non-Metastatic Renal Cell Carcinoma in Latin America and Spain: A Multicentric Analysis

Background: Renal cell carcinoma (RCC) is a lethal neoplasia. Data from Latin America are scarce, and the distinct ethnic origins of this population could affect predictive or prognostic factors. Objective: We aim to describe a large cohort of non-metastatic renal cell carcinoma, identifying the demographic, clinical, and pathological prognostic factors for survival. Methods: We used a multi-institutional retrospective cohort involving 5,670 patients who underwent radical or partial nephrectomy across seven Latin American countries and Spain from 1980 to 2016. The variables were compared, and Kaplan–Meier curves were used to estimate the overall survival (OS) and cancer-specific 

Clinical Trials Corner

A Phase 3 Randomized Study Comparing Perioperative Nivolumab vs Observation in Patients with Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

Status: Recruiting identifier: NCT03055013
Sponsor: National Cancer Institute (NCI) with Canadian Cancer Trials Group as Collaborators
Enrollment: 805

Rationale: Despite multiple studies evaluating adjuvant therapy in patients with localized RCC after nephrectomy, largely involving vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs), there remains no standard adjuvant systemic therapy that increases overall survival. While a number of adjuvant trials are underway to determine if there is a role for immune checkpoint inhibitor therapy in treatment of localized RCC, it is hypothesized that neoadjuvant PD-1 priming may be necessary to maximize efficacy. Thus, the PROSPER RCC trial is a novel trial involving perioperative nivolumab in patients with RCC undergoing nephrectomy.

Study Design: This Phase 3 study enrolls patients with clinical stage > T2 or node positive M0 RCC of any histology or patients with oligometastatic disease that can be resected or definitively treated. A tumor biopsy is mandatory prior to randomization. Patients randomized to one arm of the trial will receive two doses of perioperative nivolumab prior to nephrectomy, followed by 9 months of adjuvant nivolumab after nephrectomy. Patients randomized to the other, control arm of the trial will undergo nephrectomy followed by observation. Patients will be stratified by clinical T stage, node positivity, and histology.

Endpoints: The primary endpoint of the trial is recurrence free survival (RFS), assessed up to 10 years. The secondary endpoints include overall survival (OS), RFS for patients with clear cell RCC, and incidence of toxicity. The study also plans to evaluate the primary tumor’s expression of PD-L1 as well as the expression of PD-L1 on tumor tissue at time of recurrence, among other potential correlative studies.

Comments: This multi-center NCI-sponsored trial continues to require the engagement of investigators treating patients with RCC. As mentioned, there is no adjuvant therapy established to prolong overall survival in patients with localized RCC. While sunitinib has been demonstrated to improve progression-free survival, toxicity concerns with long-term VEGF TKI use remains a major concern. Thus, the role of immune checkpoint inhibitor therapy in this context is critical. However, more importantly, unlike the other adjuvant immune checkpoint inhibitor trials, PROSPER RCC asks important questions about the tumor immune microenvironment and the impact of the primary tumor on the effects of nivolumab. Recent amendment to the protocol now allows for patients with oligometastatic disease as long as all sites of metastases are surgically resected or definitively treated within 12 weeks of nephrectomy. Another amendment now requires core tumor biopsy for patients randomized to the nivolumab arm only, rather than both arms of the trial. These amendments should further encourage patient enrollment.