Background

The recent LATITUDE trial showed that Abiraterone plus Prednisolone (AP) combined with androgen deprivation therapy (ADT) significantly improved overall survival of patients with hormone-sensitive metastatic prostatic cancer. We conducted a study aims to evaluate whether AP plus ADT is a cost-effective strategy from Hong Kong perspective.

Methods

The current cost-effectiveness analysis (CEA) considered the reported efficacy of AP in the large-scale randomized clinical trial (LATITUDE) that recruited 1,917 patients of advanced prostate cancer, among which 1,002 had metastatic disease. Using a deterministic Markov model with probabilistic sensitivity analysis (PSA) for accounting parameter uncertainty, AP plus ADT was compared with ADT-alone in patients with metastases across a 20-year time horizon. Quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) were applied as the primary outcomes. The study took Hong Kong’s societal perspective and the WHO’s recommendation of 3 times the local gross domestic product (GDP) per capita (USD$43,530/HKD$339,531 in 2016) was used as the threshold of cost-effectiveness.

Results

The ICER of adding AP on top of ADT was USD$183,003 (median, 95% central range [CR] USD$148,780-235,632; approximately HKD$1,427,425, CR HKD$1,160,480-1,837,926) per QALY gained. Referring to the WHO’s recommended cost-effective threshold, AP plus ADT was not a cost-effective strategy compared with the current ADT-alone standard care strategy. The combined strategy of AP plus ADT, however, would be cost-effective if the cost of AP were reduced to USD$3,116 (median, approximately HKD$24,304) per cycle, which is around 72% of its current price in Hong Kong public hospital.

Conclusions

Despite the survival benefit and that Hong Kong is well-developed with high global ranking in GDP per capita, adding AP to ADT is not recommended as a cost-effective treatment in metastatic hormone sensitive prostatic cancer in Hong Kong setting.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Androgen deprivation therapy (ADT) is the most important primary treatment for locally advanced or metastatic prostate cancer. However, due to the limited curative effect of a single treatment of ADT, combined therapy strategies are usually indicated. Although nearly all prostate cancer patients initially respond to ADT, almost all patients with hormone-sensitive prostate cancer (HSPC) progress to castration-resistant prostate cancer (CRPC) after several years of ADT.Currently, however, there is no unequivocal prediction model about the time of progression to CRPC.

Methods

A total of 185 patients with prostate cancer who had received ADT as the primary therapy at our institution, from 2003 to 2014, were retrospectively enrolled. The following clinical variables were included in the analysis: age, clinical TNM stage, Gleason score (GS), risk groups of prostate cancer, prostate-specific antigen (PSA) at the initiation of ADT, PSA nadir after ADT, velocity of PSA decline, and the time to PSA nadir. Cox proportional hazards regression models were calculated to estimate effects of these variables on the time of progression to CRPC.

Results

On univariate and multivariate analyses, the presence of distant metastasis before ADT (Hazard Ratio (HR), 6.030; 95% confidence interval (CI), 3.229–11.263; P =.001), higher PSA nadir (HR, 1.185; 95% CI, 1.080–1.301; P =.001), a velocity of PSA decline >11 ng/ml*mon (HR, 2.124; 95% CI, 1.195–3.750; P =.001), and a time to PSA nadir ≤ 9 months (HR, 0.276; 95% CI, 0.162-0.469; P =.004) were significantly associated with an increased risk of progression to CRPC.Table: 262O

Univariable and multivariable analyses of risk factors of progression to CRPC after androgen deprivation therapy

Conclusions

Patients with a rapidly decreasing PSA level in the initial phase of ADT are more likely to progress to CRPC. Our findings provide a practical approach to screen patients during ADT for early identification of those likely to progress to CRPC, allowing treatment to be modified to improve outcomes.

Legal entity responsible for the study

Guangjie Ji

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Abiraterone (AA), enzalutamide (ENZ) and docetaxel (DOC) have been shown to improve survival as first-line systemic therapy in metastatic castrate resistant prostate cancer (mCRPC). However, no specific guidelines exist on how best to sequence these treatments. This preliminary observational study will compare prescribing patterns, baseline characteristics and outcomes in Australian patients receiving these therapies first line.

Methods

Data was collected from ePAD, a multi-centre collaboration database which captures information regarding mCRPC patients in major health centres across Australia. Chi square statistics and ANOVA were used to compare differences in baseline demographics and first-line treatment choice. Progression-free survival was performed using the Kaplan Meier method.

Results

The first 100 patients enrolled in the database were available for analysis. Of these, 71 received first line therapy with AA (n = 13), ENZ (n = 32) and DOC (n = 26). The median age of start of treatment was younger in the DOC group (72 years), compared with AA (74.5) or ENZ (81, p = 0.096). Baseline ECOG, co-morbidities, Gleason score and presence of metastatic disease at diagnosis were statistically similar between cohorts. The DOC cohort was found to have a lower median PSA at diagnosis (17.5 μg/L), compared to AA (115) and ENZ (27, p = 0.514). Median progression-free survival among groups was significantly different (AA: 14.7 months; ENZ: 13.8; DOC: 8, p-value = 0.0292).

Conclusions

Baseline demographics were found to be similar among groups, suggesting specific patient factors did not heavily influence prescribing patterns. ENZ was used more commonly as a first line systemic therapy. A tendency to start DOC at a younger age is likewise seen. Longer PFS is demonstrated with AA, but this must be interpreted within the limitations of a small cohort size. We aim to present updated data with the growth of the database.

Legal entity responsible for the study

Walter and Eliza Hall Institute of Medical Research

Funding

Astellas, Amgen and Janssen

Disclosure

C. Pezaro: Honoraria from Janssen, Astellas, Sanofi and Pfizer Payment for advisory boards with Novartis and Pfizer Education travel support from Pfizer, Amgen, Astellas and Janssen, B. Tran: Honoraria, Consulting and Research Funding from Astellas, Janssen, Amgen, Astra Zeneca, Tolmar Australia

All other authors have declared no conflicts of interest.

Background

The impact of neoadjuvant chemotherapy (NAC) on oncological outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC) remains unclear. The aim of the present study was to investigate the oncological outcomes of platinum-based NAC for locally advanced UTUC.

Methods

A total of 426 patients who underwent radical nephroureterectomy at five medical centers between January 1995 and April 2017 were examined retrospectively. Of 426, 234 patients were treated as a high-risk disease (cT3–4 or cN+) with or without NAC. NAC regimens were selected based on eligibility of cisplatin. We retrospectively evaluated tumor response, post-therapy pathological downstaging, lymphovascular invasion (LVI), and prognosis stratified by a NAC use. Multivariate Cox regression analysis was performed for independent factors for prognosis.

Results

Of 234 patients, 101 patients received NAC (NAC group) and 133 patients did not (Ctrl group). The regimens in the NAC group included gemcitabine and carboplatin (75%), and gemcitabine and cisplatin (21%). Pathological downstaging in the primary tumor was significantly higher in the NAC group than in the Ctrl group. NAC for locally advanced UTUC significantly prolonged progression-free, cancer-specific survival. Multivariate Cox regression analysis using an inverse probability of treatment weighted (IPTW) method showed NAC was selected as an independent predictor for prolonged progression-free, cancer-specific survival. However, the influence of NAC on overall survival was not statistically significant.

Conclusions

The platinum-based NAC for locally advanced UTUC potentially improves oncological outcomes. Further prospective studies are needed to clarify the clinical benefit of NAC for locally advanced UTUC.

Clinical trial identification

UMIN000027611.

Legal entity responsible for the study

University Hospital Medical Information Network (UMIN) Center

Funding

None

Disclosure

All authors have declared no conflicts of interest.