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Observational Study
. 2020 Dec 28;15(12):e0244462.
doi: 10.1371/journal.pone.0244462. eCollection 2020.

Observational study on time on treatment with abiraterone and enzalutamide

Giuseppe Fallara  1   2   3 , Ingela Franck Lissbrant  4 , Johan Styrke  5 , Francesco Montorsi  1   2 , Hans Garmo  3   6 , Pär Stattin  3
Affiliations
Observational Study

Observational study on time on treatment with abiraterone and enzalutamide

Giuseppe Fallara et al. PLoS One. .

Abstract

Introduction: The aim of this study was to assess time on treatment with abiraterone and enzalutamide, two androgen receptor targeted (ART) drugs, the impact on time on treatment of time interval without drug supply between prescription fillings, and adherence to treatment.

Material and methods: By use of data from The National Prostate Cancer Register, The Prescribed Drug Registry and the Patient Registry, time on treatment with the abiraterone and enzalutamide was analyzed in all men with castration resistant prostate cancer (CRPC) in Sweden 2015-2019. Three time intervals between consecutive fillings, i.e. time without drug supply, were assessed. Adherence to the treatment was evaluated by use of the Medication Possession Ratio. Kaplan Meier analysis and multivariable Cox regression model were used to assess factors affecting time on treatment.

Results: Between January 2015 and October 2019, 1803 men filled a prescription for abiraterone and 4 534 men filled a prescription for enzalutamide. With a time interval of 30 days or less between two fillings, median time on treatment was 4.9 months (IQR 2.6-11.7) for abiraterone and 8.0 months (IQR 3.6-16.4) for enzalutamide. In sensitivity analyses, allowing for no more than 14 days without drug supply between fillings, median time on treatment was 3.9 months (IQR 2.1-9.0) for abiraterone and 5.9 months (IQR 2.8-12.1) for enzalutamide. Allowing for any time period without drug between fillings, median time on treatment was 5.7 months (IQR 2.7-14.0) for abiraterone and 9.8 months (IQR 4.4-21.0) for enzalutamide. Adherence to treatment was above 90% for both drugs.

Conclusion: Time on treatment with abiraterone and enzalutamide was shorter in clinical practice than in randomized controlled trials and varied almost two-fold with time interval without drug. Adherence to treatment was high. The main limitation of our study was the lack of data on use of chemotherapy.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Possible scenarios for filled prescriptions in the Prescribed Drug Registry.
Legend: A: Stop date if 14 days are allowed between period covered by drug supply. B: Stop date if 30 days are allowed between period covered by drug supply. C: Stop date if no restriction on time interval between fillings is applied. The Defined daily dose (DDD) corresponds to two pills per day for abiraterone and to one per day for enzalutamide, and a package usually supplies drugs for 28 days. There is sometimes a time period without drug supply. This time period allows for a putative immortal time bias. To limit this bias we used 30 days as the longest time period without drug supply (using the 14 days and no restriction as sensitivity analysis). DDD = Defined Daily Dose.
Fig 2
Fig 2. Time on treatment with abiraterone and enzalutamide.
Legend: Cumulative incidence of drug stop using time interval between fillings of 14-day, 30-day or no restriction. For definition of drug stop see Fig 1.
Fig 3
Fig 3
Time on treatment stratified by age at drug initiation (A), primary treatment (B), and androgen deprivation therapy duration before ART (C).
See this image and copyright information in PMC

References

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