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For patients with renal cell carcinoma (RCC), belzutifan, a hypoxia inducible factor inhibitor, not only demonstrated improved progression-free survival compared with everolimus in the trial, but the patient-reported outcomes were also better, according to data presented at the .

The study compared the two drugs in patients with previously treated advanced RCC. Patient-reported outcomes were evaluated with the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index-Disease Related Symptoms (FKSI-DRS) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire.

Time to deterioration (TTD) was a chief outcome, and patients experienced meaningfully longer TTD with belzutifan versus everolimus as measured by both assessment tools, reported Thomas Powles, MD, of Barts Cancer Center in London, and colleagues. With the FKSI-DRS, for example, TTD was not reached with belzutifan compared with approximately 12 months with everolimus (HR 0.53, P<0.001).

"Overall, patient-reported outcome results indicate better disease-specific symptoms and quality of life among patients treated with belzutifan compared with everolimus," the researchers concluded.

Co-author Brian Rini, MD, chief of Clinical Trials at Vanderbilt Ingram Cancer Center in Nashville, offered his perspective on the results in the following interview.

Why are tolerability and quality of life important considerations for advanced or refractory RCC?

Rini: Belzutifan is known as a very well-tolerated drug, and the quality-of-life data support this notion. In the refractory RCC space, because drugs are generally considered non-curative, patient tolerance and quality of life are most important.

What is it about the mechanism of action of belzutifan that could explain the better patient-reported outcomes?

Rini: Belzutifan targets HIF [hypoxia inducible factor] very specifically, and this likely explains why the side effects are more limited, which leads to better quality-of-life outcomes.

What do you see as the main clinical implications of the trial?

Rini: Belzutifan can provide objective responses and disease control in a subset of refractory RCC patients and is generally well tolerated.

The manufacturer filed a new drug application for adults with RCC who experienced disease progression after PD-1/PD-L1– and VEGFR-targeted therapies. Are there any other potential indications for belzutifan?

Rini: Belzutifan is being tested in a variety of earlier settings, including adjuvant therapy and front- and second-line RCC in combination with other drugs. The biology of RCC supports its utility in earlier disease.

Do you have any advice on how to optimize the use of belzutifan in patients with RCC?

Rini: I think we are still figuring this out. Careful attention to toxicity including anemia, which is easily treated with growth factors, and hypoxia is critical. Figuring out which patients will respond best is critical and requires further investigation.

Read the study here and expert commentary about it here.