Survival Outcomes, Prostate-specific Antigen Response, and Tolerance in First and Later Lines of Enzalutamide Treatment for Metastatic Castration-resistant Prostate Cancer: A Real-World Experience in Hong Kong

Lin

et al. 2020

Sci Rep

We evaluated the efficacy of second-line hormonal therapy for treatment of metastatic castrationresistant prostate cancer (mcRpc) in a real-world retrospective study. We conducted a populationbased real-world cohort study of 258 mCRPC patients between 2014 and 2018 using the Chang Gung Research Database (CGRD) of Taiwan. The second-line hormonal therapy included abiraterone acetate and enzalutamide. The clinical efficacy outcomes were overall survival (OS) and prostate-specific antigen (PSA) doubling time. The median PSA level was also assessed. In total, 223 mCRPC patients who underwent second-line hormonal therapy met all of the inclusion and exclusion criteria for this study. Among them, 65 (29.1%) patients were in the PSA response group and 158 (70.9%) were in the non-response group. The median age was 72.9 years. The median OS was 12.3 months (range: 9.9-19.9 months) and 9.6 months (range: 5.3-15.9 months) in the response and non-response groups, respectively, and the respective PSA doubling times were 9.0 months (range: 4.4-11.6 months) and 3.9 months (range: 2.2-9.1 months), with a median follow-up period of 10.5 months. A significantly longer median oS was seen in the pSA response group. this real-world database study demonstrated that clinical outcomes of second-line hormonal therapy were better in patients with a pSA response. further studies are warranted to achieve a better understanding of second-line hormonal therapy for mcRpc in Asian populations.Androgen deprivation therapy (ADT) has been a mainstay of treatment for advanced prostate cancer (PCa) 1 . Eventually, patients with PCa will progress to castration-resistant prostate cancer (CRPC). In recent years, second-line hormonal therapies for metastatic CRPC (mCRPC) have become available, including abiraterone acetate (AA) and enzalutamide 2,3 . Both of them prolonged overall survival in patients with mCRPC who had disease progression.A randomized double-blind controlled study (COU-AA-301) of metastatic CRPC patients post-chemotherapy showed that AA therapy significantly increased overall survival (OS) and radiographic progression-free survival (rPFS) in comparison to placebo 2 . The COU-AA-302 trial also showed that AA increased OS and rPFS in metastatic CRPC patients pre-chemotherapy 4 . Meanwhile, the AFFIRM and PREVAIL studies showed that enzalutamide had significant benefits on OS and rPFS in metastatic CRPC patients, both post-and pre-chemotherapy 3,5 . AA and enzalutamide for treatment of metastatic CRPC have been approved by the Taiwan Food and Drug

Section: Discussionmentioning

confidence: 97%

Second-line Hormonal Therapy for the Management of Metastatic Castration-resistant Prostate Cancer: a Real-World Data Study Using a Claims Database

Lin

et al. 2020

Sci Rep

“…We published two reports of real-life experience using abiraterone and enzalutamide in the Hong Kong Chinese population. Apart from slightly higher rates of hypertension and peripheral oedema with abiraterone [ 32 ], and hypertension and fatigue with enzalutamide [ 33 ], our mCRPC patients experienced similar rates of severe adverse events as those in pivotal studies [ 34 , 35 , 36 , 37 ]. The differences might, to some extent, be attributable to our inclusion of patients with higher baseline prostate-specific antigen (PSA) levels and Gleason scores, as well as reporting differences (fatigue was physician-reported in real-life, but self-reported in trials).…”

Section: Drug Tolerability In Asian Patientsmentioning

confidence: 87%

Ethnic Pharmacogenomic Differences in the Management of Asian Patients with Metastatic Prostate Cancer

Poon

Chan

et al. 2022

Cancers

Self Cite

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

“…In the AFFIRM trial, pretreatment ALP and LDH levels were correlated with PSA value [27]. Moreover, ALP level prior to enzalutamide treatment has been proven to be a strong predictor of progression-free survival in a real-world cohort [28]. Furthermore, it has been observed in several mCRPC series that the higher the LDH value before treatment with enzalutamide or abiraterone, the poorer the progression-free survival [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

High Tumor Burden Predicts Poor Response to Enzalutamide in Metastatic Castration-Resistant Prostate Cancer Patients

Hsieh

Chiang

et al. 2021

Cancers

To assess the predictive value of tumor burden on the biochemical response, and radiological response in Taiwanese metastatic castration-resistant prostate cancer (mCRPC) patients receiving enzalutamide. The mCRPC patients treated with enzalutamide were recruited from three hospitals. High tumor burden (HTB) was classified as metastases at either appendicular bone or visceral organ. Good prostate-specific antigen (PSA) response was defined as PSA reduction of 80%. In this cohort, there were 104 (54.2%) HTB patients and 88 (45.8%) with low tumor burden (LTB). Compared to LTB patients, fewer HTB patients had good PSA response (odds ratio: 0.43, range: 0.22–0.87, p = 0.019) and fewer radiological response (complete and partial remission) (odds ratio: 0.78, range: 0.36–1.68, p = 0.52) to enzalutamide. The disease control rate which also contained stable disease, was still lower in HTB (76.0%) than LTB group (92.9%, OR: 0.24, range: 0.07–0.77, p = 0.016) in the multivariable model. In addition, HTB patients had significantly shorter progression–free survival duration than did LTB patients (median: 8.3 vs. 21.6 months, log-rank test p = 0.003) in the univariable analysis. The tumor burden before the use of enzalutamide was associated with treatment outcomes. HTB reduced PSA response rate, radiological response rate and progression-free survival duration.