LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy.

The first-in-class, small molecule HIF-2α inhibitor, belzutifan, has demonstrated promising antitumor activity in previously treated patients with clear cell renal cell carcinoma (RCC). HIF-2α also regulates VEGF expression and is involved in resistance to anti-VEGF therapy. This study describes the rationale and design for a randomized, phase III study evaluating efficacy and safety of belzutifan plus the tyrosine kinase inhibitor (TKI) lenvatinib versus the TKI cabozantinib in patients with advanced RCC progressing after anti-PD-1/PD-L1 therapy in the first- or second-line setting or as adjuvant therapy. Considering the unmet need for effective and tolerable treatment of advanced RCC following immune checkpoint inhibitors, belzutifan plus lenvatinib may have a positive benefit/risk profile. Clinical Trial Registration: NCT04586231 (ClinicalTrials.gov).

The future of perioperative therapy in advanced renal cell carcinoma: how can we PROSPER?

Patients with high-risk renal cell carcinoma (RCC) experience high rates of recurrence despite definitive surgical resection. Recent trials of adjuvant tyrosine kinase inhibitor therapy have provided conflicting efficacy results at the cost of significant adverse events. PD-1 blockade via monoclonal antibodies has emerged as an effective disease-modifying treatment for metastatic RCC. There is emerging data across other solid tumors of the potential efficacy of neoadjuvant PD-1 blockade, and preclinical evidence supporting a neoadjuvant over adjuvant approach. PROSPER RCC is a Phase III, randomized trial evaluating whether perioperative nivolumab increases recurrence-free survival in patients with high-risk RCC undergoing nephrectomy. The neoadjuvant component, intended to prime the immune system for enhanced efficacy, distinguishes PROSPER from other purely adjuvant studies and permits highly clinically relevant translational studies.

Real-world evidence in metastatic renal cell carcinoma.

Real-world evidence has played an important role in expanding our knowledge on the treatment and prognostication of advanced renal cell carcinoma. This type of data has been particularly helpful in providing a better understanding of groups that are traditionally excluded from randomized controlled trials. The International mRCC Database Consortium (IMDC) represents the largest collection of real-world data on patients with advanced kidney cancer treated with targeted therapies. The IMDC prognostic model has been used to stratify patients in contemporary clinical trials and to provide risk-directed treatment selection in everyday clinical practice. More recently, it has been shown to predict response to first-line combination immunotherapy in the phase III CheckMate 214 clinical trial. In this review, we highlight the real-world evidence associated with the treatment of mRCC. We focus on first-line therapy, as well as second-line and third-line therapeutic options, including novel immuno-oncology agents. We also address the real-world evidence for the use of cytoreductive nephrectomy in advanced renal cell carcinoma in the targeted therapy era.

Adult patient perspectives on clinical trial result reporting: A survey of cancer patients.

BACKGROUND: The provision of study results to research participants is supported by pediatric and adult literature. This study assessed adult cancer patient preferences surrounding aggregate result disclosure to study participants. METHODS: A 46-item questionnaire was given to 250 adult cancer patients who had participated in oncology trials at a single center. Respondents answered questions surrounding their preferences for timing, content, and modality of communication for dissemination of study results. RESULTS: Questionnaire completion rate was 76% (189/250). Most patients (92%) strongly felt a right to know study results. Patients preferred result dissemination via letter for trials with positive outcomes, but preferred in-person clinic visits for negative outcomes. Despite this, a majority of participants (59%) found letters acceptable to inform participants of negative results. Only a minority (36%) of the participants found Internet-based disclosure acceptable for negative trial results. Unfortunately, very few patients (8%) recalled having received the results for a study they participated in, and of these patients, less than half fully understood the results they were given. CONCLUSION: Most clinical trial participants feel they have a right to study result disclosure, regardless of trial outcome. In-person visits are preferred for negative results, but more feasible alternatives such as letters were still acceptable for the majority of participants. However, Internet-based disclosure was not acceptable to most participants in oncology trials. Time and cost allocations for result disclosure should be considered during grant and ethics board applications, and clear guidelines are required to help researchers share the results with patients.