A Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) Analysis of Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma (aRCC)

Shah, Ruchitbhai; Botteman, Marc; Solem, Caitlyn T; Luo, Linlin; Doan, Justin; Cella, David; Motzer, Robert J.

doi:10.1016/j.clgc.2019.05.010

Cited by 11 publications

(10 citation statements)

References 48 publications

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“…After the failure of second‐line therapy, 88% of nivolumab‐treated patients could receive subsequent therapy, including nivolumab TBP, and this conversion rate was higher than that of mTT‐treated patients (55%). This might be induced by the better tolerability to nivolumab compared with mTT, as previously reported 3,19,20 . Even in cases of disease progression, a relatively maintained general condition might allow for further treatment with nivolumab.…”

Section: Discussionmentioning

confidence: 79%

Efficacy of nivolumab versus molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma: Real‐world data from two Japanese institutions

et al. 2020

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ObjectivesTo compare the efficacy of nivolumab with that of molecular‐targeted therapy as a second‐line therapy for metastatic renal cell carcinoma using real‐world data.MethodsWe retrospectively evaluated patients who received nivolumab or molecular‐targeted therapy after the failure of first‐line molecular‐targeted therapy between January 2008 and December 2019 at two Japanese institutions. Progression‐free survival and overall survival after the initiation of second‐line therapy were calculated using the Kaplan‐Meier method and compared using the log‐rank test. Objective response rate was assessed based on the Response Evaluation Criteria in Solid Tumors version 1.1.ResultsAmong 159 patients, 43 (27%) and 116 (73%) patients received nivolumab and molecular‐targeted therapy as second‐line therapy, respectively. During follow up (median 11.1 months), 129 (81%) and 98 (62%) patients had disease progression and died, respectively. Progression‐free survival was comparable between the two treatments (median 5.06 vs 5.95 months, P = 0.881), whereas overall survival was significantly longer with nivolumab than with molecular‐targeted therapy (not reached vs 13.0 months, P = 0.0008). Multivariate analysis further showed that nivolumab therapy was an independent favorable factor for overall survival (hazard ratio 0.33, P = 0.0007). In 151 patients with eligible radiographic data, the objective response rate was significantly higher in nivolumab than in molecular‐targeted therapy (n = 14/41 [34%] vs n = 20/110 [18%], P = 0.0485).ConclusionsReal‐world data analysis suggests superior efficacy of nivolumab over molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma.

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Section: Discussionmentioning

confidence: 79%

Efficacy of nivolumab versus molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma: Real‐world data from two Japanese institutions

et al. 2020

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“…The majority of previously published Q-TWiST analyses in advanced RCC focused on first-line treatments [17] , [18] , [19] , [20] . Shah et al [21] compared quality-adjusted survival time (measured using the Q-TWiST method) between nivolumab and everolimus in the second or third line in advanced RCC using CheckMate 025 data. They found that treatment with nivolumab was associated with a significant Q-TWiST gain of 3.3 mo (relative gain 14%) versus everolimus [21] .…”

Section: Discussionmentioning

confidence: 99%

“…Shah et al [21] compared quality-adjusted survival time (measured using the Q-TWiST method) between nivolumab and everolimus in the second or third line in advanced RCC using CheckMate 025 data. They found that treatment with nivolumab was associated with a significant Q-TWiST gain of 3.3 mo (relative gain 14%) versus everolimus [21] . In the phase 3 METEOR trial, cabozantinib was compared with everolimus in patients with advanced RCC who progressed after previous tyrosine-kinase inhibitor treatment [22] .…”

Section: Discussionmentioning

confidence: 99%

Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) for Lenvatinib plus Everolimus Versus Everolimus Monotherapy in Patients with Advanced Renal Cell Carcinoma

Lee

Yin

Smith

et al. 2021

European Urology Open Science

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Background The lenvatinib (LEN) plus everolimus (EVE) combination demonstrated improved progression-free survival over everolimus alone in a phase 2 trial (Study-205). Objective To compare quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) between LEN + EVE and EVE alone among patients with advanced renal cell carcinoma (RCC) following one prior antiangiogenic therapy. Design, setting, and participants This was a post hoc analysis of Study-205. Outcome measurements and statistical analysis Survival time was partitioned into three mutually exclusive health states: time with grade 3/4 toxicity (TOX); time before disease progression and without grade 3/4 toxicity (TWiST); and time after disease progression (REL). The mean time in each state was weighted by utility measures and summed to calculate Q-TWiST. Nonparametric bootstrapping generated 95% confidence intervals (CIs). In the base case, utility for TWiST, TOX, and REL was assigned as 1.0, 0.5, and 0.5, respectively. Sensitivity analyses applied alternative utility values for REL, TOX, and TWiST. A relative gain in Q-TWiST of ≥10% and ≥15% has been established as clinically important and clearly clinically important, respectively. Results and limitations Patients receiving LEN + EVE ( n = 51) had a significant mean Q-TWiST gain of 3.7 mo (14.7 vs 11.0 mo; 95% CI for difference 1.3–6.3), with a relative gain of 24% compared to EVE alone. In a sensitivity analysis using alternative utility values for TWiST (varied from 0.55 to 0.9) with utility set to 0.5 for both TOX and REL, the relative Q-TWiST gain was maintained (ranging from 11.0% to 21.2%; all significant) across varying utility values. Limitations include the sample size, the absence of utility estimates, and the length of adverse events from the trial. Conclusions LEN + EVE showed a significant and clearly clinically important improvement in quality-adjusted survival time versus EVE alone. Patient summary Patients with advanced kidney cancer who had received other previous treatments experienced a clearly clinically important improvement in quality survival time when treated with lenvatinib plus everolimus compared to everolimus alone.

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“…7 In previously treated patients with renal cell carcinoma, lenvatinib plus everolimus improved Q-TWiST relative to everolimus alone owing to an increased TWIST, 8 whereas nivolumab improved Q-TWiST relative to everolimus owing to increased TWIST and decreased TOX. 9 Therefore, an improvement in Q-TWIST by treatments for patients with renal cell carcinoma may be due to increases in TWiST with or without significant decreases in states with a lower utility (ie, TOX and REL).…”

Section: Introductionmentioning

confidence: 99%

Q-TWiST Analysis of Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma in the TIVO-3 Study

Szarek

Needle

Rini

et al. 2021

Clinical Genitourinary Cancer

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In TIVO-3, tivozanib increased progression-free survival relative to sorafenib in patients with metastatic renal cell carcinoma. In the current analysis, tivozanib also increased quality-adjusted time without symptoms of disease and toxicity (Q-TWiST). As an outcome that integrates the quantity and quality of survival, Q-TWiST may be considered an alternative patient-centered measure of tivozanib benefit in renal cell carcinoma. Background: In TIVO-3, tivozanib increased progression-free survival with no difference in overall survival relative to sorafenib as third-or fourth-line therapy in patients with metastatic renal cell carcinoma. We applied quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) methods to quantify the net health benefits of tivozanib, in the presence of similar survival, when compared with sorafenib. Methods: The mean Q-TWiST was calculated by applying utility coefficients of 0.5, 1.0, and 0.5 to the 36-month restricted mean health states of time with toxicity (TOX), TWiST, and time after progression/relapse, respectively. The relative Q-TWiST gain was defined as the mean absolute Q-TWiST difference divided by the sorafenib mean overall survival. Results: The mean TWiST was longer for tivozanib than for sorafenib, mean time after progression/relapse was shorter for tivozanib, with no difference in mean TOX. Mean Q-TWiST was 15.04 months and 12.78 months for tivozanib and sorafenib, respectively ( P = .0493). The tivozanib relative gain was 11.2%. Discussion: Tivozanib increased Q-TWiST relative to sorafenib, pr imar ily through an increase in TWiST, which is generally considered to be the highest utility state. Conclusion: Q-TWiST may be considered an alternative patient-centered measure of benefit of tivozanib in as a third-or fourth-line therapy in patients with renal cell carcinoma. Clinical trial information: NCT02627963

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A Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) Analysis of Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma (aRCC)

Cited by 11 publications

References 48 publications

Efficacy of nivolumab versus molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma: Real‐world data from two Japanese institutions

Efficacy of nivolumab versus molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma: Real‐world data from two Japanese institutions

Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) for Lenvatinib plus Everolimus Versus Everolimus Monotherapy in Patients with Advanced Renal Cell Carcinoma

Q-TWiST Analysis of Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma in the TIVO-3 Study

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