The effect of medication nonadherence on progression-free survival among patients with renal cell carcinoma

To examine how observed medication nonadherence to 2 second-line, oral anticancer medications (axitinib and everolimus) affects progression-free survival (PFS) among patients with renal cell carcinoma.

We used an adherence-exposure-outcome model to simulate the impact of adherence on PFS. Using a pharmacokinetic/pharmacodynamic (PK/PD) population model, we simulated drug exposure measured by area under the plasma concentration-time curve (AUC) and minimum blood or trough concentration (Cmin) under 2 scenarios: 1) optimal adherence and 2) real-world adherence. Real-world adherence was measured using the medication possession ratios as calculated from health insurance claims data. A population PK/PD model was simulated on individuals drawn from the Medical Expenditure Panel Survey (MEPS), a large survey broadly representative of the US population. Finally, we used previously published PK/PD models to estimate the effect of drug exposure (i.e., Cmin and AUC) on PFS outcomes under optimal and real-world adherence scenarios.

Average adherence measured using medication possession ratios was 76%. After applying our simulation model to 2164 individuals in MEPS, drug exposure was significantly higher among adherent patients compared with nonadherent patients for axitinib (AUC: 249.5 vs. 159.8 ng×h/mL, P<0.001) and everolimus (AUC: 185.4 vs. 118.0 µg×h/L, P<0.001). Patient nonadherence in the real world decreased the expected PFS from an optimally adherent population by 29% for axitinib (8.4 months with optimal adherence vs. 6.0 months using real-world adherence, P<0.001) and by 5% (5.5 vs. 5.2 months, P<0.001) for everolimus.

Nonadherence by renal cell carcinoma patients to second-line oral therapies significantly decreased the expected PFS.

Cancer management and research. 2017 Nov 29*** epublish ***

Jason Shafrin, Jeffrey Sullivan, Jacquelyn W Chou, Michael N Neely, Justin F Doan, J Ross Maclean

Precision Health Economics, Los Angeles, CA, USA., Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA.


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