Abstract
Purpose: The effectiveness of poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitor olaparib for metastatic castration-resistant prostate cancer (MCRPC) with multiple loss-of-function alterations in genes that are involved in DNA repair has been demonstrated. We aimed to evaluate the cost-effectiveness of genomic test-directed olaparib on MCRPC from the US payer perspective. Methods: A partitioned survival model was adopted to project the disease course of MCRPC had at least one gene alteration in BRCA1, BRCA2 and ATM (Scenario A) and has alterations in any of all 15 prespecified genes (Scenario B) after next-generation sequencing test. The efficacy and toxicity data were gathered from the PROfound trial. Clinical probabilities related to survival were estimated from the reported survival probabilities in each PROfound group. Cost and health preference data were derived from the literature. The incremental cost-effectiveness ratio (ICER) was measured. Subgroup analysis and sensitivity analysis were performed for exploring the model uncertainties. Results: Olaparib yielded an additional 0.063 and 0.068 of quality-adjusted life year (QALY) with the augmented cost of $7,382 and saved the cost of $ 1,980 compared to standard care in scenario A and B, respectively, which yielded an ICER of $116,903/QALY and a cost-saving option. The lower weekly cost related to olaparib treatment led to the dominant findings in scenario B. The varied results between scenario A and B could be partly explained by different the number need to screen for identifying eligible patients who could be administered with olaparib, which sharply augmented the costs of the olaparib arm in scenario A. Subgroup analysis and sensitivity analysis revealed the results were generally robust in both of two scenarios. Conclusion: The genomic test-directed olaparib is a preferred option compared with standard care strategy for men with MCRPC who had any of all 15 prespecified genes.
Highlights
Prostate cancer is one of the most common malignancies in men and a major cause of cancer deaths, accounting for 5.4% of the disease burden of all neoplasms, as reported by the GBD 2017 DALYs and HALE Collaborators, 2017 (2018)
The genomic test-directed olaparib is a preferred option compared with standard care strategy for men with Metastatic castration-resistant prostate cancer (MCRPC) who had any of all 15 prespecified genes
The PROfound trial reported the efficacy and safety of olaparib for men with MCRPC who had any of all 15 prespecified genes that had direct or indirect role in homologous recombination repair and who had disease progression while receiving a new hormonal agent
Summary
Prostate cancer is one of the most common malignancies in men and a major cause of cancer deaths, accounting for 5.4% of the disease burden of all neoplasms, as reported by the GBD 2017 DALYs and HALE Collaborators, 2017 (2018). Deleterious aberrations in genes involved in repairing DNA damage, such as BRCA1, BRCA2 and ATM, were found in up to 30% of patients with prostate cancer (Bishop et al, 2019). The PROfound trial reported the efficacy and safety of olaparib for men with MCRPC who had any of all 15 prespecified genes that had direct or indirect role in homologous recombination repair and who had disease progression while receiving a new hormonal agent (de Bono et al, 2020; Hussain et al, 2020). The olaparib treatment seemed to be an attractive option for men who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair
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