Patient-reported outcomes in advanced RCC favour belzutifan over everolimus

Treatment with belzutifan helps patients with previously treated advanced renal cell carcinoma (RCC) achieve better disease-specific symptoms and quality of life (QoL) compared with everolimus, according to the patient-reported outcome (PRO) data from the phase III LITESPARK-005 trial.

Belzutifan was associated with significantly longer time to deterioration of quality of life, as reported by patients using either the disease-related scale of the FKSI (FKSI-DRS*; not reached vs 11.99 months; hazard ratio [HR], 0.53, 95 percent confidence interval [CI], 0.41–0.69; p<0.0001) or the global health scale of the EORTC QLQ-C30** (19.35 vs 10.19 months; HR, 0.75, 95 percent CI, 0.58–0.96; p=0.0185). [ASCO GU 2024, abstract 361]

Least squares mean changes in FKSI-DRS and QLQ-C30 scores from baseline to week 17 indicated that such measures remained stable with belzutifan (least squares mean, –0.17 and 0.28, respectively) but worsened with everolimus (least squares mean, –1.62 and –6.11, respectively), reported first study author Dr Thomas Powles of the Barts Cancer Institute, Queen Mary University of London, London, UK.

Powles noted a trend toward belzutifan performing slightly better than everolimus, with less deterioration in QLQ-C30 scores of physical functioning (–4.75 vs –7.22; difference, 2.47, 95 percent CI, –0.59 to 5.54; p=0.1134) and role functioning (–4.89 vs –9.10; difference, 4.21, 95 percent CI, 0.06–8.37; p=0.0470) over the 17-week period. As for the symptom scores, belzutifan also outperformed everolimus, with less deterioration or greater improvement in fatigue, dyspnoea, appetite loss, and diarrhoea, among others.

The PRO analysis included 366 of 374 patients assigned to receive belzutifan 120 mg orally once daily (median treatment duration 7.6 months) and 354 of 372 patients assigned to receive everolimus 10 mg orally once daily (median treatment duration 3.9 months). These patients had unresectable locally advanced or metastatic ccRCC with disease progression after 1 to 3 prior regimens, including an immune checkpoint inhibitor and antiangiogenic therapies.

FKSI-DRS and EORTC QLQ-C30 questionnaires were administered electronically at day 1 of weeks 1, 3, 5, and 9, then every 4 weeks thereafter, at treatment discontinuation, and at day 30 after the last dose. Powles pointed out that the rates of FKSI-DRS and QLQ-C30 completion were high at more than 90 percent at baseline and more than 55 percent at week 17.

“Along with improvements in progression-free survival and objective response rate [seen with belzutifan in the initial analysis], these [PRO] findings support the benefit of belzutifan in patients with advanced clear cell RCC after prior immune checkpoint and antiangiogenic therapies,” Powles said. [Ann Oncol 2023;34:S1329-S1330]

Challenges in interpretation

Acknowledging the challenges in interpreting QoL data in cancer trials, Powles pointed to the lack of established thresholds for defining clinically meaningful changes in QoL parameters.

He noted that many PRO analyses are exploratory, with not all QoL measures being equally relevant to all patients. Furthermore, it can be difficult to distinguish which symptoms are related to treatment and which are directly caused by the disease itself.

“Overall, [QoL analyses] probably are better at assessing the patient journey than these black-and-white [Common Terminology Criteria for Adverse Events],” he said.

Powles underscored the need to modernize QOL assessment tools, believing that electronic devices could prove more valuable than traditional, lengthy questionnaires, which have been in use for 30 or 40 years.

*Functional Assessment of Cancer Therapy–Kidney Symptom Index Disease-Related Symptoms

**European Organization for the Research and Treatment of Cancer Core Quality of Life questionnaire