Daniel Heng, MD, highlights final LITESPARK-011 results in advanced ccRCC

In this video, Daniel Heng, MD, MPH, FRCPC, discusses the final analysis of the phase 3 LITESPARK-011 trial (NCT04586231), which evaluated belzutifan (Welireg) plus lenvatinib (Lenvima) vs cabozantinib (Cabometyx) in patients with advanced clear cell renal cell carcinoma (ccRCC) following anti-PD-(L)1 therapy.¹ These results were presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain. Heng is head of medical oncology at the Arthur J.E. Child Comprehensive Cancer Centre in Calgary, Alberta and a clinical professor of medicine at the University of Calgary.

The final analysis showed that the progression-free survival (PFS) benefit with belzutifan plus lenvatinib was maintained, with a median PFS of 14.8 months vs 10.8 months with cabozantinib (HR, 0.74; 95% CI, 0.62 to 0.88; nominal 1-sided P = 00035). The objective response rate was 53.1% with the combination vs 40.2% with cabozantinib (estimated difference, 12.9%; 95% CI, 5.8 to 19.8; nominal P = .0002).

“[It’s] important to put into context that in the real world, in the second [or] third line setting, we are expecting response rates of 20%, maybe 30%, and progression-free survival of 7 to 8 months with other agents. The fact that now we get to 52% for overall response rates and progression-free survival of 14.8 months, it pushes the needle forward for our patients with metastatic renal cell carcinoma.”

Median overall survival (OS) also favored the combination at 33.7 months vs 28.6 months, representing a 5.1-month difference; however, this result did not meet the prespecified statistical significance boundary (HR, 0.85; 95% CI, 0.70-1.03; 1-sided P = .04689; prespecified boundary, 0.0223).

Heng discusses how clinicians can interpret the OS findings alongside the sustained PFS benefit and higher response rate, emphasizing the potential clinical relevance of the observed survival difference despite the lack of statistical significance. He also highlights the longer median duration of response with belzutifan plus lenvatinib compared with cabozantinib (22.0 vs 11.9 months) and considers whether additional follow-up could clarify the OS findings. Grade 3 or higher treatment-emergent adverse events occurred in 85.4% of patients receiving the combination and 83.0% of those receiving cabozantinib.

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REFERENCE

1. Heng DYC, McDermott RS, Park SH, et al. Final analysis of the phase 3 LITESPARK-011 study: Belzutifan (bel) plus lenvatinib (len) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti–PD-(L)1 therapy. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026, Madrid, Spain. Abstract 35870. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2026_abstracts/3587O.html.pdf