The UroOnc Minute: LITESPARK-022 and Adjuvant Therapy in ccRCC, with Wesley Yip, MD

Welcome back to The UroOnc Minute!

In this episode of The UroOnc Minute, host Adam B. Weiner, MD, welcomes Wesley Yip, MD, of City of Hope for a focused discussion on the phase 3 LITESPARK-022 trial (NCT05239728), highlighting its potential to reshape the adjuvant treatment landscape for clear cell renal cell carcinoma (ccRCC). The conversation centers on the emerging role of combination therapy with pembrolizumab (Keytruda) and belzutifan (Welireg) in patients at elevated risk of recurrence following nephrectomy, including those with advanced pathologic features or resected metastatic disease.

Data from the LITESPARK-022 trial were recently presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California.¹

Yip provides important clinical context by revisiting the foundation established by KEYNOTE-564 (NCT03142334), which led to FDA approval of adjuvant pembrolizumab after demonstrating a disease-free survival (DFS) benefit over placebo.² Building on this, LITESPARK-022 evaluates whether the addition of belzutifan—a HIF-2α inhibitor—can further improve outcomes. Interim results suggest a meaningful improvement in DFS with the combination approach (HR, 0.72; 95% CI, 0.59 to 0.87; P = .0003) compared with pembrolizumab plus placebo, reinforcing growing interest in intensifying therapy for appropriately selected high-risk patients.

The discussion also underscores the importance of thoughtful patient selection and toxicity management in this setting. Although combination therapy may offer enhanced efficacy, Yip emphasizes that these treatments are not without risk, with adverse events such as immune-related toxicities, anemia, hypoxia, and fatigue requiring careful monitoring and counseling.

As the field awaits overall survival data and potential regulatory decisions, the episode highlights a central clinical challenge: balancing therapeutic benefit with tolerability while tailoring treatment decisions to individual patient risk. Looking ahead, ongoing trials exploring additional adjuvant combinations signal continued momentum toward optimizing outcomes in RCC.

REFERENCES

1. Choueiri TK, Motzer RJ, Karam JA, et al. Adjuvant pembrolizumab plus belzutifan versus pembrolizumab for clear cell renal cell carcinoma (ccRCC): The randomized phase 3 LITESPARK-022 study. ). Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA418. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16925?presentation=256660

2. Choueiri TK, Tomczak P, Park SH, et al. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024;390(15):1359-1371