New Meta-analysis Backs Efficacy in nccRCC
A new systematic review and meta-analysis have reinforced the growing evidence base for immunotherapy-based treatment combinations in non–clear cell renal cell carcinomas (nccRCCs)—a rare, heterogeneous group of kidney cancers historically underrepresented in clinical trials.
Drawing on 23 studies and encompassing a broad range of nccRCC subtypes, the pooled analysis demonstrated that immune checkpoint inhibitors (ICIs), particularly in combination with targeted therapies, are associated with improved clinical outcomes in the metastatic setting.
Challenges in nccRCC: A Diverse and Understudied Landscape
Unlike clear cell renal cell carcinoma, which dominates the RCC landscape and has a well-defined treatment algorithm, nccRCC includes a diverse array of histological subtypes such as papillary, chromophobe, collecting duct, and medullary carcinomas. These subtypes are notoriously challenging to treat due to their rarity, biological variability, and limited representation in prospective trials.
The review, which included data up to December 2024 from PubMed, Embase, and the Cochrane Library, evaluated outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). Studies were selected based on relevance to ICI-based therapy in nccRCC and were rigorously assessed for quality using the Newcastle-Ottawa Scale.
Key Findings: Efficacy of Immunotherapy in Focus
Pooled results revealed an ORR of 26.6% and a DCR of 57.8% across all included studies. The median PFS was 6.59 months, and the median OS was 21.11 months.
While ICIs showed effectiveness as monotherapy, combination strategies—pairing immunotherapy with agents targeting angiogenesis or mTOR pathways—were associated with superior clinical outcomes. The findings highlight a meaningful step forward in managing a population with a historically poor prognosis and limited treatment options.
Clinical Implications and the Path Forward
These data support the incorporation of ICI-based regimens into first-line treatment guidelines for metastatic nccRCC, particularly when tailored to histological subtype and individual patient characteristics. As evidence continues to grow, the need for personalised treatment approaches becomes more urgent.
“This systematic review and meta-analysis found that ICIs, particularly when combined with targeted therapies, showed promising efficacy in treating metastatic nccRCC. These findings support their integration into treatment guidelines and emphasise the importance of personalised treatment strategies,” the authors concluded.
They further stressed the need for long-term data, improved safety profiling, and biomarker-driven patient selection to refine treatment strategies and optimise outcomes.
In a disease space long defined by therapeutic uncertainty, this meta-analysis offers a data-driven direction for the future of nccRCC care.
Paper: Petrelli, F., et al. First-Line Therapy For Advanced Non–Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. JAMA Oncol. doi:10.1001/jamaoncol.2025.1891. Published online July 3, 2025. Access online here.