Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of belzutifan versus everolimus in previously treated advanced renal cell carcinoma (RCC): LITESPARK-005 (LS-005)
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Authors
Powles T.
De Velasco G.
Choueri T.
Chen G.
Xiao Y.
Shinde R.
Moneuse P.
Del Fava E.
Perini R.
Vickery D.
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2025
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Background: Belzutifan significantly prolonged progression-free survival vs. everolimus in the phase 3 LS-005 trial (NCT04195750) among patients with advanced RCC who had previously received immune checkpoint and antiangiogenic therapies. Q-TWiST is an established framework that integrates efficacy, safety, and patient health utility data into one interpretable index. This analysis applied the Q-TWiST method to quantify the net health benefits of belzutifan versus everolimus, based on the final analysis of LS-005 (15Apr2024 cutoff) Methods: Patients' survival time after randomization was divided into 3 mutually exclusive health states: Time with grade 3-4 toxicity before investigator-assessed disease progression (TOX); time without symptoms of progression or grade 3-4 toxicity (TWiST); and time from progression until death (REL, ie, relapse). In each treatment arm, Q-TWiST was calculated as the sum-product of restricted mean time spent in the three states and state-specific utility weights. Standard set of utility weights used in literature (1 for TWiST, 0.5 for TOX and REL) were considered, with threshold utility analysis performed to assess the impact of the different health state utility. Treatment effects were summarized as differences in restricted mean time spent in each state, difference in Q-TWiST, and relative gain in Q-TWiST (difference divided by everolimus mean overall survival). Bootstrap resampling was performed to obtain 95% confidence intervals (CIs) Results: With a maximum follow-up of 49 months, patients treated with belzutifan had significantly longer TWiST, significantly shorter time in REL, and numerically longer time in TOX than those treated with everolimus (Table). Mean Q-TWiST difference significantly favored belzutifan by 2.66 months (95% CI: 1.06, 4.49; relative gain: 11.32%) when applying standard utility weights. In a sensitivity analysis using the utility weights of TOX and REL varying between 0 to 1, the mean Q-TWiST difference varies from 0.54 to 4.43 months, and the associated relative gain varied from 2.28% to 18.82%. Scenario analysis using an alternative TOX definition of all-cause SAE showed minimal impact on results Conclusion(s): Belzutifan showed a statistically significant and clinically important improvement in quality-adjusted survival time compared to everolimus among patients with advanced RCC who had previously received immune checkpoint and antiangiogenic therapies..
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The oncologist