Introduction

Prostate cancer stands as the second most frequently diagnosed cancer in men and ranks fifth among the leading causes of cancer-related deaths worldwide.1 It is anticipated that the global burden of prostate cancer will escalate to 1.7 million new cases and 499,000 fatalities per year by 2030.2 As per the GLOBOCAN 2020 estimates, prostate cancer contributed to 2.1% of cancer-related mortalities in Asia in the year 2020.3 Within Thailand, prostate cancer occupies the eighth position in terms of cancer-related mortality with 3,837 deaths per year.34 The escalating incidence of prostate cancer is postulated to be a consequence of enhanced longevity and the assimilation of Westernized lifestyle practices, catalyzed by socioeconomic advancements.5 The mortality-to-incidence ratio for prostate carcinoma within Thailand is notably documented at 0.51, a contrast to the 0.09 metric observed in more medically advanced regions such as the United States. This differential in survival indices for prostate carcinoma in the Thai context may be partially attributed to the suboptimal utilization of prostate-specific antigen (PSA) diagnostic screening, relative to other nations.6 The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal, and Ovarian (PLCO) trials present compelling evidence supporting the capacity of PSA screening to mitigate prostate cancer-specific mortality.7

Androgen deprivation therapy (ADT) has been a mainstay treatment for prostate cancer, attributed to cancer cells' dependence on androgens for growth and progression. ADT has the potential to induce tumor regression and alleviate symptoms in metastatic prostate cancer patients. However, a significant proportion eventually acquire resistance to initial ADT due to a range of mechanisms, leading to a condition recognized as castration-resistant prostate cancer (CRPC).8

The understanding of resistance mechanisms in metastatic CRPC (mCRPC) has spurred the development of novel drugs aimed at treating mCRPC. The treatment landscape for mCRPC has rapidly transformed with the introduction of new therapies. The U.S. Food and Drug Administration (FDA) has approved several agents for managing mCRPC, including docetaxel, sipuleucel-T, abiraterone acetate, enzalutamide, cabazitaxel, radium-223, olaparib, etc.9

Abiraterone acetate, an active prodrug precursor to abiraterone, functions as a potent and specific inhibitor of the enzyme CYP17A1, pivotal in the androgenic biosynthetic cascade.10 The National Comprehensive Cancer Network (NCCN) guidelines advocate for the utilization of abiraterone acetate in treating CRPC as a category 1 recommendation, either before or after docetaxel therapy.11 Abiraterone acetate has demonstrated its ability to prolong survival in patients with mCRPC, initially in the mCRPC setting and subsequently in high-risk, high-volume de novo metastatic hormone-sensitive prostate cancer (mHSPC). Recommended dose of abiraterone for mCRPC is 1,000 mg orally once daily with prednisone 5 mg orally twice daily, and for mHSPC is 1,000 mg orally once daily with prednisone 5 mg orally once daily. Dose modification is required for patients with baseline moderate hepatic impairment and for patients who develop hepatotoxicity during treatment.1213 A randomized clinical trial compared low-dose abiraterone (250 mg after a low-fat meal) to a standard dose (1,000 mg, fasting) in men with mCRPC. Although noninferiority could not be established with statistical rigor because of the low power of the trial, it was supported strongly by the PSA data and by similar Pharmacodynamic (PD) effects of the low and standard doses.14 The NCCN added low-dose abiraterone with food as an acceptable alternative to the standard dose for treatment of men with prostate cancer in resource-constrained countries.11

This real-world, retrospective observational study was undertaken to assess the safety and efficacy of abiraterone in patients with metastatic prostate cancer treated with Abiratred in routine clinical practice in Thailand.

Materials and Methods

This single-center, retrospective, real-world observational clinical study compiled data from prostate cancer patients treated at Siriraj Hospital between June 2018 and April 2022. Ethical approval was granted by the Siriraj Institutional Review Board. A total of 47 patients who had received generic abiraterone (Abiratred) treatment were screened, including those with mCRPC (asymptomatic or mildly symptomatic) following failed ADT, those not yet exposed to chemotherapy, those newly diagnosed with high-risk mHSPC, or those mHSPC patients who had progressed after a docetaxel-based regimen. Complete data were accessible for 35 patients, all above 18 years old, and nonparticipants in other clinical trials. Information encompassing demographics, medical history, general examination, vital signs, comorbidities, health status, and prostate cancer-related details was gathered. Analysis involved patients with a follow-up duration of at least 6 months, concentrating on primary and secondary outcomes.

The study's primary outcome was the PSA response rate (≥ 50% decline in PSA level from baseline). Secondary outcomes included defining PSA progression-free survival (PFS) as the duration from treatment initiation until PSA progression (defined as an increase of 25% or more and an absolute increase of 2 ng/mL or more from the nadir). Additionally, disease control rate (DCR) was assessed, representing the percentage of patients with advanced or metastatic cancer who achieved complete response, partial response, or stable disease. The study also evaluated the abiraterone's safety by documenting all adverse events occurring throughout the study period, providing a detailed description of each event.

Results

The study included a population of patients presenting varying stages of advanced or metastatic prostate cancer. Most (82.9%) of the patients had mCRPC with ADT failure and were chemotherapy naive. The remaining patients were newly diagnosed with high-risk mHSPC (14.3%) or had mCRPC that had progressed post a docetaxel-based chemotherapy regimen (2.9%). The entire study group consisted of 35 male patients, with a median age of 73 years (range: 53–85 years). Each patient received abiraterone monotherapy at different dosage regimens: 77.1% received 1,000 mg once daily, 11.4% received 750 mg once daily, 5.7% received 500 mg once daily, and 5.7% received 250 mg once daily with a low-fat meal. At the commencement of abiraterone treatment, the median PSA level was 11.6 ng/mL. Demographic particulars, baseline characteristics, and imaging assessment findings are detailed in Table 1.

Primary Outcomes

The study's primary endpoint was the PSA response rate (≥ 50% decline in PSA level from baseline). Among the 35 patients included in the study, 23 (65.7%) achieved this response (Fig. 1).

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Fig. 1: Waterfall plot of percent change in prostate-specific antigen (PSA) level from baseline to last evaluation. Note: Values of PSA percentage changes for 3 patients were outliers and were not included in the graph above.

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Discussion

This real-world clinical study showcased the efficacy of abiraterone acetate, an inhibitor of androgen biosynthesis, among patients with advanced/metastatic prostate cancer. The primary endpoint, involving a reduction in PSA serum levels from baseline, coupled with favorable prespecified secondary outcomes, substantiates the antitumor activity of abiraterone.

In the COU-AA-302 phase III trial, abiraterone acetate (1,000 mg) along with prednisone (5 mg twice daily) was compared with placebo plus prednisone in patients with mCRPC who had not undergone prior chemotherapy. Abiraterone exhibited improvement in radiographic PFS, overall survival, and delayed clinical deterioration and initiation of chemotherapy in individuals with mCRPC.1516 Following these results, the U.S. FDA approved abiraterone acetate, indicating a significant breakthrough and a major stride in treating patients with mCRPC.17 The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment, and follow-up of prostate cancer (2022) endorse abiraterone (ESMO-MCBS v1.1 score 4) as a primary treatment choice for asymptomatic/mildly symptomatic patients with chemotherapy-naive mCRPC (grade I, level A).18 Similarly, the NCCN guidelines (2024) classify abiraterone as a category 1 preferred treatment for patients with first-line mCRPC.11

In our study, 65.7% of the patients attained the primary endpoint of PSA response rate (defined as a reduction of ≥ 50% in PSA levels). Previous research has likewise documented rates of PSA response to abiraterone treatment in patients with mCRPC that are comparable. In the COU-AA-302 trial, the PSA response rate was 62%.15 In a recent real-world experience within the Southeast Asian cohort, the PSA response rate with abiraterone was noted to be 58%.19 Likewise, Facchini et al reported that a significant proportion of patients (56%) exhibited a PSA response upon initiating abiraterone therapy.20 Leibowitz-Amit et al identified a confirmed PSA response to abiraterone in 44 out of 108 assessable mCRPC patients (41%, 95% confidence interval [CI]: 31–50%).21

Numerous studies have validated the clinically meaningful advantage presented by abiraterone acetate in terms of the median PSA PFS within advanced/metastatic prostate cancer. Koninckx et al reported a median time to PSA progression and PFS of 4.4 months (p = 0.003) and 5.1 months (p = 0.034), respectively, among patients who underwent abiraterone treatment prior to chemotherapy.22 Similarly, Raju et al observed that the PSA PFS was 5 months (95% CI: 3.3–6.7; p = 0.022) for individuals undergoing abiraterone treatment in the context of mCRPC.23 In our study, the PSA PFS at 6 months demonstrated a rate of 65.6%.

The effectiveness of CRPC treatments on disease response are intricately linked to patients' adherence to the prescribed dosage regimens. Research has demonstrated that patients exhibit higher medication adherence and a reduced risk of dose reduction when treated with abiraterone as compared to enzalutamide therapy.24 During the Prostate Cancer Consensus Conference for Developing Countries, the recommended best practice for mCRPC involves an abiraterone regimen of 1,000 mg along with prednisone 5 mg/d. However, in settings with limited resources, an acceptable alternative is the utilization of abiraterone 250 mg accompanied by fatty foods and prednisone 5 mg/d.25

In clinical trials, abiraterone has exhibited a generally favorable safety profile, yet potential adverse effects linked to its mechanism of action are possible. Many studies have documented grade 1 to 2 adverse events associated with abiraterone, including fluid retention, asthenia, elevated transaminases, and hypertension.26 A meta-analysis conducted by Moreira et al indicated an increased risk of cardiovascular events with abiraterone treatment.27 Within our study, occurrences of adverse events such as E. coli septicemia, herpes simplex virus infection in the buttock region, urinary tract infection with septic shock, hypertensive urgency, and closed fracture of the neck of the right femur were observed. However, most of these incidents were not found to be directly linked to abiraterone treatment. It is noteworthy that treatment with abiraterone can induce mineralocorticoid-associated adverse events due to the reduction in glucocorticoid production, thereby leading to an augmented production of adrenocorticotropic hormone and mineralocorticoid excess. Consequently, this can contribute to the onset or exacerbation of hypertension, hypokalemia, and fluid retention in certain patients.2829

Bjartell et al conducted a prospective observational study using the Prostate Cancer Registry, assessing mCRPC patients treated with abiraterone acetate plus prednisone or prednisolone as first-line or post-docetaxel therapy. This study also examined the efficacy parameters such as PSA response rate, PSA PFS, and DCR as those of our study. Findings indicated abiraterone's efficacy within real-world settings, with notable PSA responses and stable disease proportions. Comparable adverse event reporting highlights abiraterone's safety profile. These results collectively underscore abiraterone's effectiveness and safety, reinforcing its significance in mCRPC treatment. Both studies observed a PSA response rate of 65.7%, with close alignment in PSA PFS (8.9 months by Bjartell et al, 6 months in our study) and DCR (71.4% in both studies). This coherence supports abiraterone's role as a valuable mCRPC treatment option.30

Cindolo et al also evaluated the safety and efficacy of abiraterone acetate in the context of mCRPC within real-world settings. Comparing with our study, both demonstrated the effectiveness of abiraterone acetate, with comparable PSA response rates of 49% at 12 weeks in Cindolo et al's study and 65.7% in our study. Additionally, both studies indicated a positive DCR, with Cindolo et al reporting a proportion of 71.4% and our study showing 71.4%. The findings from both studies collectively support the notion that abiraterone acetate is effective in treating mCRPC in real-world scenarios, highlighting its value as a treatment option.31

This study has several limitations that need to be taken into account. First, it is a single-center, retrospective study. Second, due to the limited number of eligible patients from a single center, we were unable to provide an analysis of a larger sample size. Due to retrospective nature of this study and limited sample size, it was difficult to provide accurate Kaplan–Meier curves from the data. Despite these limitations, the outcomes of this real-world study are consistent with the conclusions drawn from earlier randomized controlled trials and real-world investigations. Our findings provide evidence that generic abiraterone (Abiratred) is both well-tolerated and effective for patients with advanced/metastatic prostate cancer. These results may have important implications for the use of generic abiraterone in clinical practice.

Conclusion

This real-world study provides evidence that generic abiraterone (Abiratred) is both well-tolerated and effective for patients with advanced or metastatic prostate cancer, making it a promising option in real-world clinical settings.