Overview of the First-Line nccRCC Treatment Landscape
Panelists discuss recent advances in non–clear cell renal cell carcinoma (nccRCC) treatment, highlighting the emerging role of immunotherapy plus tyrosine kinase inhibitor (TKI) combinations—particularly lenvatinib and pembrolizumab—in improving response rates, progression-free survival, and overall survival across diverse subtypes, while emphasizing individualized care and proactive management.
Recent advancements have brought encouraging news for patients with nccRCC, a subtype historically challenging to treat. Unlike clear cell RCC, non–clear cell variants—such as papillary, chromophobe, translocation, and unclassified types—have had limited data guiding treatment decisions. Previously, many patients were treated with a single-agent TKI, notably cabozantinib, which demonstrated promising activity. However, single-agent TKIs often did not yield long-term durable responses, and more effective options were needed.
Two key studies have shaped the current approach to nccRCC treatment by evaluating immunotherapy-based combinations. One smaller trial combined cabozantinib with nivolumab and showed response rates around 50%, with progression-free survival (PFS) near 13 months and overall survival (OS) around 18 months. A larger international phase 2 study assessed lenvatinib combined with pembrolizumab, enrolling approximately 150 patients across multiple non–clear cell subtypes, including chromophobe. This study reported similar response rates near 50%, but more notably, it revealed a median PFS of 18 months and an impressive median OS exceeding 40 months. These results suggest that immunotherapy combined with targeted therapy can significantly improve outcomes and potentially extend survival for these patients.
In clinical practice, immunotherapy plus TKI combinations have become the preferred first-line treatment for nccRCC, with lenvatinib and pembrolizumab frequently favored due to robust data. It is essential to individualize treatment, considering subtype and patient factors. Setting clear expectations about potential adverse effects, ensuring effective communication, and emphasizing proactive management of symptoms are critical to optimizing outcomes. Incorporation of these regimens into national guidelines has improved accessibility by influencing insurance coverage and providing community oncologists with evidence-based options for this rare and diverse cancer subtype.
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