ArticleeLife2022
Evolution-based mathematical models significantly prolong response to abiraterone in metastatic castrate-resistant prostate cancer and identify strategies to further improve outcomes.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 116 citations in OpenAlex.
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15 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Background: Abiraterone acetate is an effective treatment for metastatic castrate-resistant prostate cancer (mCRPC), but evolution of resistance inevitably leads to progression. We present a pilot study in which abiraterone dosing is guided by evolution-informed mathematical models to delay onset of resistance. Methods: In the study cohort, abiraterone was stopped when PSA was <50% of pretreatment value and resumed when PSA returned to baseline. Results are compared to a contemporaneous cohort who had >50% PSA decline after initial abiraterone administration and met trial eligibility requirements but chose standard of care (SOC) dosing. Results: 17 subjects were enrolled in the adaptive therapy group and 16 in the SOC group. All SOC subjects have progressed, but four patients in the study cohort remain stably cycling (range 53-70 months). The study cohort had significantly improved median time to progression (TTP; 33.5 months; p<0.001) and median overall survival (OS; 58.5 months; hazard ratio, 0.41, 95% confidence interval (CI), 0.20-0.83, p<0.001) compared to 14.3 and 31.3 months in the SOC cohort. On average, study subjects received no abiraterone during 46% of time on trial. Longitudinal trial data demonstrated the competition coefficient ratio ( Conclusions: Incorporation of evolution-based mathematical models into abiraterone monotherapy for mCRPC significantly increases TTP and OS. Computer simulations with updated parameters from longitudinal trial data can estimate intratumoral evolutionary dynamics in each subject and identify strategies to improve outcomes. Funding: Moffitt internal grants and NIH/NCI U54CA143970-05 (Physical Science Oncology Network).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.