Stereotactic Radiotherapy for Oligoprogression in Metastatic Renal Cell Cancer Patients Receiving Tyrosine Kinase Inhibitor Therapy: A Phase 2 Prospective Multicenter Study.

BACKGROUND: Despite the paucity of prospective evidence, stereotactic radiotherapy (SRT) is increasingly being considered in the setting of oligoprogression to delay the need to change systemic therapy. OBJECTIVE: To determine the local control (LC), progression-free survival (PFS), cumulative incidence of changing systemic therapy, and overall survival (OS) after SRT to oligoprogressive metastatic renal cell carcinoma (mRCC) lesions in patients who are on tyrosine kinase inhibitor (TKI) therapy. DESIGN, SETTING, AND PARTICIPANTS: A prospective multicenter study was performed to evaluate the use of SRT in oligoprogressive mRCC patients. Patients with mRCC who had previous stability or response after ≥3 mo of TKI therapy were eligible if they developed progression of five of fewer metastases. Thirty-seven patients with 57 oligoprogressive tumors were enrolled. INTERVENTION: Oligoprogressive tumors were treated with SRT, and the same TKI therapy was continued afterward. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Competing risk analyses and the Kaplan-Meir methodology were used to report the outcomes of interest. RESULTS AND LIMITATIONS: The median duration of TKI therapy prior to study entry was 18.6 mo; 1-yr LC of the irradiated tumors was 93% (95% confidence interval [CI] 71-98%). The median PFS after SRT was 9.3 mo (95% CI 7.5-15.7 mo). The cumulative incidence of changing systemic therapy was 47% (95% CI 32-68%) at 1 yr, with a median time to change in systemic therapy of 12.6 mo (95% CI 9.6-17.4 mo). One-year OS was 92% (95% CI 82-100%). There were no grade 3-5 SRT-related toxicities. CONCLUSIONS: LC of irradiated oligoprogressive mRCC tumors was high, and the need to change systemic therapy was delayed for a median of >1 yr. PATIENT SUMMARY: The use of stereotactic radiotherapy in metastatic kidney cancer patients, who develop growth of a few tumors while on oral targeted therapy, can significantly delay the need to change to the next line of drug therapy.

The efficacy and safety of sunitinib given on an individualised schedule as first-line therapy for metastatic renal cell carcinoma: A phase 2 clinical trial.

BACKGROUND: Sunitinib is administered on a rigid schedule that may not be optimal for all patients. We hypothesised that toxicity-driven dose and schedule changes would optimise drug exposure and outcome for each patient. MATERIALS AND METHODS: In a phase 2 trial, 117 patients with metastatic clear cell renal cell cancer were started on sunitinib 50 mg/day with the aim to treat for 28 days. Treatment breaks were reduced to 7 days. Sunitinib dose and the number of days on therapy were individualised based on toxicity aiming for ≤ grade II toxicity with dose escalation in patients with minimal toxicity. The null hypothesis for the primary end-point was a progression-free survival (PFS) of 8.5 months based on a study with similar eligibility criteria. RESULTS: The null hypothesis was rejected (p < 0.001) with a median PFS of 12.5 months (95% confidence interval [CI]: 9.6-16.5). The median overall survival was 38.5 months (95% CI: 28.3-not reached). The objective response rate (46.1%) and stable disease rate (38.5%) translated into a clinical benefit for 84.6% of patients with no decline in quality of life scores during therapy. Fewer patients were dose reduced (26.5% vs. 50%) or discontinued due to toxicity (7.7 vs. 18-20%) compared to standard sunitinib dosing, and 20 (18.4%) patients were dose escalated to 62.5 mg (12) and 75 mg (8) with a wide individual variation in the optimal dose and treatment duration. CONCLUSIONS: Individualised sunitinib therapy is feasible, safe and an effective method to manage toxicity with one of the best efficacy seen for oral vascular endothelial growth factor inhibitors in metastatic renal cell carcinoma. CLINICALTRIALS. GOV IDENTIFIER: NCT01499121.

Using the Delphi technique to improve clinical outcomes through the development of quality indicators in renal cell carcinoma.

PURPOSE: Optimal quality of care is needed for ideal outcomes. In renal cell carcinoma (RCC), there is a lack of information defining optimal care. This is particularly important in RCC, with increased complexity of care and a need for coordination among providers. The goal of this study was to identify quality indicators (QIs) and measures of quality care across the RCC disease spectrum. MATERIALS AND METHODS: A modified Delphi technique was used to select QIs that are relevant and practical to RCC care. This technique involved an expert panel of 13 urologic and medical oncologists who participated in two e-mail questionnaires and an in-person meeting to review and prioritize potential QIs. These potential QIs were identified from a systematic literature review or were suggested by panel members. RESULTS: From 233 literature citations, 34 possible QIs were identified; 24 additional potential QIs were suggested. A final set of 23 QIs was established. These are distributed across the RCC disease spectrum as follows (number of QIs in parentheses): screening (n=1), diagnosis/prognosis (n=3), surgical for localized disease (n=6), surgery for advanced disease (n=3), systemic therapy (n=6), and follow-up (n=2). In addition, two QIs related to survival outcomes (overall and progression-free survival) were selected. CONCLUSION: A systematic, consensus-based approach was used to determine relevant QIs in RCC care. These 23 QIs will provide a means of evaluating the quality of RCC care in an effort to improve outcomes in patients. The next step will be to establish a means of measuring each QI based on defined or yet-to-be-defined benchmarks.