Impact of brain metastases on systemic renal cell carcinoma treatment outcomes: A systematic literature review

Abstract

Introduction

Brain metastases (BrM) are a negative prognostic factor in renal cell carcinoma (RCC) populations. Patients with RCC and BrM (RCC BrM + ) may receive systemic therapy and/or brain-targeted (local) treatment. We performed a systematic literature review to identify clinical trials and non-interventional studies reporting data on BrM impact on systemic treatment outcomes in patients with RCC.

Methods

We systematically searched the MEDLINE and Embase databases in January 2024 for publications reporting efficacy/effectiveness and/or safety/tolerability outcomes by BrM status from phase 2 and phase 3 clinical trials and non-interventional studies of systemic RCC therapies. Data were extracted from publications meeting predefined criteria (PROSPERO registration, CRD42023494896) and reported in accordance with PRISMA guidelines.

Results

Sixty-two publications (of 651 screened) were eligible (4 from prospective trials) and included 4,637 patients with RCC BrM + treated with systemic therapy. The most evaluated systemic therapies were sunitinib, nivolumab, ipilimumab + nivolumab, cabozantinib and sorafenib. Tolerability was generally consistent with known safety profiles in RCC trial populations. In the clinical trials, systemic treatment benefits for patients with RCC BrM + were equivocal. In non-interventional studies, survival was generally poorer in patients with RCC BrM + than reference groups (overall/BrM–). Survival and intracranial control benefits in patients with RCC BrM + were reported for some multimodal (systemic plus local) treatment strategies. There were no robust comparative data to guide systemic treatment selection.

Conclusion

We identified a need for robust data on intracranial and extracranial responses to systemic therapy in patients with RCC BrM+, taking into account prior local therapy exposure.