Cost Effectiveness of Systemic Treatment Intensification for Metastatic Hormone-sensitive Prostate Cancer: Is Triplet Therapy Cost Effective?

BACKGROUND AND OBJECTIVE: There has been a shift toward systemic treatment intensification for men with metastatic hormone-sensitive prostate cancer (mHSPC). Recent trials have demonstrated the efficacy of triplet therapy with an androgen receptor signalling inhibitor (ARSI), docetaxel, and androgen deprivation therapy (ADT). However, ARSI treatment is expensive. The objective was to determine the cost effectiveness of current treatments strategies for men with mHSPC. METHODS: We developed a Markov state-transition model to simulate outcomes for men with newly diagnosed mHSPC. For the simulation, patients were entered in the model in the mHSPC disease state before progressing to castration-resistant disease and finally dying from prostate cancer. Costs were calculated from a USA health sector perspective in 2022 US dollars. Deterministic and probabilistic sensitivity analyses were conducted to account for uncertainty in the parameter estimates. We also performed scenario analyses for costs in the UK and Australian health sectors. KEY FINDINGS AND LIMITATIONS: Treatment intensification with doublet and triplet therapy resulted in an improvement in quality-adjusted survival for all strategies in comparison to ADT monotherapy. However, only docetaxel doublet therapy was cost effective at standard thresholds, with an incremental cost-effectiveness ratio of $13 647. The cost of ARSIs needed to be discounted by 47-70% before they were cost effective. Only medication costs impacted the model results. If the generic price for abiraterone acetate is used, then triplet therapy with abiraterone is the best-value option. Similar results were obtained for analyses for the UK and Australian health sectors. CONCLUSIONS AND CLINICAL IMPLICATIONS: Treatment intensification with ARSIs in men with mHSPC results in better quality-adjusted survival but is not cost effective according to standard thresholds. The costs of these medications would need to be heavily discounted before they are cost effective. The cost of generic ARSIs, once available, would render these strategies cost effective. PATIENT SUMMARY: This report examines whether increasing the number of systemic drugs used to treat a patient's metastatic hormone-sensitive prostate cancer is cost effective for the health care system. We found that the additional cost of triplet therapy does not justify the increase in patient benefit.

Real-world clinical outcomes and cost estimates of metastatic castration-resistant prostate cancer treatment: does sequencing of taxanes and androgen receptor-targeted agents matter?

INTRODUCTION: Health economic outcomes of real-world treatment sequencing of androgen receptor-targeted agents (ARTA) and docetaxel (DOC) remain unclear. MATERIAL AND METHODS: Data from the electronic Castration-resistant Prostate cancer Australian Database (ePAD) were analyzed including median overall survival (mOS) and median time-to-treatment failure (mTTF). Mean total costs (mTC) and incremental cost-effectiveness ratios (ICER) of treatment sequences were estimated using the average sample method and Zhao and Tian estimator. RESULTS: Of 752 men, 441 received ARTA, 194 DOC, and 175 both sequentially. Of participants treated with both, first-line DOC followed by ARTA was the more common sequence (n = 125, 71%). mOS for first-line ARTA was 8.38 years (95% CI: 3.48, not-estimated) vs. 3.29 years (95% CI: 2.92, 4.02) for DOC. mTTF was 15.7 months (95% CI: 14.2, 23.7) for the ARTA-DOC sequence and 18.2 months (95% CI: 16.2, 23.2) for DOC-ARTA. In first-line, ARTA cost an additional $13,244 per mTTF month compared to DOC. In second-line, ARTA cost $6726 per mTTF month. The DOC-ARTA sequence saved $2139 per mTTF compared to ARTA-DOC, though not statistically significant. CONCLUSION: ICERs show ARTA had improved clinical benefit compared to DOC but at higher cost. There were no significant cost differences between combined sequences.

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901).

OBJECTIVES: To determine the activity and safety of lutetium-177 (177 Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. PARTICIPANTS AND METHODS: ENZA-p (ANZUP 1901) is an open-label, randomized, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177 Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177 Lu-PSMA-617 doses are allowed, informed by Day-92 Gallium-68 (68 Ga)-PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate-specific antigen (PSA) progression-free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health-related quality of life, adverse events and cost-effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68 Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high-risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68 Ga-PSMA PET at baseline, Days 15 and 92, and at progression, and 18 F-fluorine deoxyglucose (18 F-FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga-PSMA and 18 F-FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two-sided type-1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. RESULTS AND CONCLUSION: The combination of 177 Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.