Dataset Information

Cost-Effectiveness Analysis of Fourth- or Further-Line Ripretinib in Advanced Gastrointestinal Stromal Tumors.

ABSTRACT:

Background

The INVICTUS trial assessed the efficacy and safety of ripretinib compared with placebo in the management of advanced gastrointestinal stromal tumors.

Method

We used a Markov model with three health states: progression-free disease, progression disease and death. We parameterized the model from time-to-event data (progression-free survival, overall survival) of ripretinib and placebo arms in the INVICTUS trial and extrapolated to a patient's lifetime horizon. Estimates of health state utilities and costs were based on clinical trial data and the published literature. The outcomes of this model were measured in quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was tested via univariate and probabilistic sensitivity analyses.

Results

The base-case model projected improved outcomes (by 0.29 QALYs) and additional costs (by $70,251) and yielded an ICER of $244,010/QALY gained for ripretinib versus placebo. The results were most sensitive to progression rates, the price of ripretinib, and health state utilities. The ICER was most sensitive to overall survival. When overall survival in the placebo group was lower, the ICER dropped to $127,399/QALY. The ICER dropped to $150,000/QALY when the monthly cost of ripretinib decreased to $14,057. Probabilistic sensitivity analyses revealed that ripretinib was the cost-effective therapy in 41.1% of simulations at the willingness-to-pay (WTP) threshold of $150,000.

Conclusion

As the fourth- or further-line therapy in advanced gastrointestinal stromal tumors, ripretinib is not cost-effective in the US. Ripretinib would achieve its cost-effectiveness with a price discount of 56% given the present effectiveness.

SUBMITTER: Liao W

PROVIDER: S-EPMC8685288 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRipretinib is a novel switch-control kinase inhibitor that inhibits KIT and PDGFRA signaling. In the INVICTUS phase 3 trial, ripretinib increased median progression-free survival and prolonged overall survival vs. placebo in ≥ fourth-line advanced GIST. Here, we report prespecified analysis of quality of life (QoL) as assessed by patient-reported outcome (PRO) measures and an exploratory analysis evaluating the impact of alopecia on QoL.MethodsIn the INVICTUS trial (NCT03353753), QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; physical function, role function, overall health, and overall QoL) and the EuroQoL 5-Dimension 5-Level (EQ-5D-5 L; visual analogue scale). Analysis of covariance (ANCOVA) models compared changes in scores from baseline to treatment cycle 2, day 1 within and between ripretinib and placebo. Within the ripretinib arm, repeated measures models assessed the impact of alopecia on QoL.ResultsPatients receiving ripretinib maintained QoL (as assessed by the EORTC QLQ-C30 and EQ-5D-5 L PRO measures) from baseline to cycle 2, day 1 whereas QoL declined with placebo, resulting in clinically significant differences between treatments (nominal P < 0.01). The most common treatment-emergent adverse event with ripretinib was alopecia; however, QoL was similarly maintained out to treatment cycle 10, day 1 in patients receiving ripretinib who developed alopecia and those who did not.ConclusionPRO assessments in the INVICTUS trial suggest that patients on ripretinib maintain their QoL out to C2D1, unlike patients receiving placebo. Longitudinal QoL was maintained for patients receiving ripretinib out to cycle 10, day 1 (approximately 8 months; past the point of median progression-free survival with ripretinib [6.3 months]), even if the patients developed alopecia.Trial registrationClinicalTrials.gov Identifier: NCT03353753 ; first posted: November 27, 2017.

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