• ASCO 2018: Perspective on Balancing Toxicities in the Treatment of mHSPC

    Chicago, IL (UroToday.com) Celestia Higano, MD, gave a talk on the topic of treatment toxicities in patients with metastatic hormone-sensitive prostate cancer (MHSPC). Dr. Higano began with the most important question in this topic, on how to decide which therapy to use in MHSPC. One of the options is to decide by volume of metastatic disease. 
    Published June 7, 2018
  • ASCO 2018: Treatment of mHSPC and Implications for Subsequent Management

    Chicago, IL (UroToday.com) Neeraj Agarwal provided a comprehensive overview of the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Three general topics were reviewed – the current standard of care for men with (mHSPC), the role of definitive therapy of primary prostate cancer (PC ) in the setting of mHSPC, and the implication of the upfront use of novel therapies on subsequent treatments in the setting of metastatic castrate-resistant prostate cancer (mCRPC).
    Published June 20, 2018
  • ASCO GU 2018: Enzalutamide vs Bicalutamide in Combination with Androgen Deprivation in mHSPC

    San Francisco, CA (UroToday.com) Dr. Vaishampayan and colleagues presented results of their randomized trial assessing enzalutamide vs bicalutamide in combination with androgen deprivation in metastatic hormone sensitive prostate cancer. Over the past several years, phase III trials have demonstrated that the addition of abiraterone or docetaxel improves overall survival (OS) for men with metastatic hormone sensitive prostate cancer (mHSPC) [1-4]. However, the clinical outcomes with early enzalutamide in mHSPC are unknown. Thus, the objective of this study was to compare the combinations of enzalutamide (Arm A) or bicalutamide (Arm B) each with LHRH analogue therapy in mHSPC.
    Published February 9, 2018
  • ASCO GU 2019: ARCHES Trial-Phase 3 Study of ADT with Enzalutamide in mHSPC

    San Francisco, CA (UroToday.com) The introduction of androgen-axis targeted therapies has drastically altered the landscape of advanced prostate cancer. Abiraterone acetate (AA) and Enzalutamide (ENZA) have been driving the change, and have been utilized in even earlier stages of advanced prostate cancer. Two recent studies, STAMPEDE, and LATITUDE,1,2 have established the utility of adding AA + prednisone to ADT among men with high‐risk, hormone‐naïve PCa.
    Published February 15, 2019
  • ASCO GU 2019: Cost-Effectiveness of Metastasis-Directed Therapy in the Setting of Oligometastatic Hormone-Sensitive Prostate Cancer

    San Francisco, CA (UroToday.com) Dr. Parikh discussed that previously published data have suggested there may be a benefit for metastasis-directed therapy in patients with oligorecurrent hormone-sensitive prostate cancer. 
    Published February 15, 2019
  • Astellas and Pfizer Announce Positive Top-Line Results from Phase 3 ARCHES Trial of XTANDI® (enzalutamide) in Men with Metastatic Hormone-Sensitive Prostate Cancer

    San Francisco, CA USA (UroToday.com) -- Astellas Pharma Inc. President and CEO: Kenji Yasukawa, Ph.D., and Pfizer Inc. announced that the Phase 3 ARCHES trialevaluating XTANDI® (enzalutamide) plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC) met its primary endpoint, significantly improving radiographic progression-free survival (rPFS) versus ADT alone. The preliminary safety analysis of the ARCHES trial appears consistent with the safety profile of XTANDI in previous clinical trials in castration-resistant prostate cancer (CRPC). Detailed results will be submitted for presentation at an upcoming medical congress.
    Published December 20, 2018
  • Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer

    BACKGROUND: Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone.

    METHODS: We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of the body-surface area every 3 weeks for six cycles) or ADT alone. 
    Published December 18, 2018
  • CUOS 2019: Is There a Role for Treating the Primary in Metastatic Hormone-sensitive Prostate Cancer

    Toronto, Ontario (UroToday.com) Dr. Robert Hamilton presented on the role of treatment of the primary tumor in the setting of metastatic hormone-sensitive prostate cancer (mHSPC).  He began his discussion providing the rationale for treating the primary tumor in mHSPC patients. This involves both clinical and biological factors. The biologic factors include:
    Published January 11, 2019
  • EAU 2019: Conclusions from Recent Oncology Meetings Regarding: Hormone Naïve Prostate Cancer

    Barcelona, Spain (UroToday.com) Dr. Nguyen presented a summary of the latest news in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Four recent major trials were summarized and discussed in this presentation:
    1. STAMPEDE – Abiraterone in low volume metastatic disease (presented in ESMO 2018)
    2. LATITUDE – Abiraterone long term update (presented in ASCO GU 2019)
    3. STAMPEDE – Prostate radiotherapy in low volume metastatic disease – (presented in ESMO 2018)
    4. ARCHES – Enzalutamide radiographic progression-free survival (presented in ASCO GU 2019)
    Published March 20, 2019
  • EAU 2019: The Medical Oncologist’s Perspective on the Treatment for Prostate Cancer

    Barcelona, Spain (UroToday.com) Dr. Silke Gillessen presented the medical oncologist’s perspective on the current and future treatment of prostate cancer. Her talk mainly focused on the role of systemic therapy in metastatic hormone-sensitive prostate cancer (HSPC) and non-metastatic and metastatic castrate-resistant prostate cancer (CRPC).
    Published March 16, 2019
  • ESMO 2018: Randomized Trial of ADT + Enzalutamide Versus ADT + Bicalutamide in Metastatic Hormone Sensitive Prostate Cancer

    Munich, Germany (UroToday.com) Enzalutamide is an androgen signaling inhibitor which prevents androgen receptor nuclear translocation and DNA binding, therefore leading to cellular apoptosis.  Enzalutamide has been largely studied in the metastatic castration-resistant population, demonstrating an overall survival benefit for patients before and after chemotherapy1,2. In an open-label, single arm, phase II study, enzalutamide was also found to be well tolerated in patients with castration-sensitive prostate cancer, with 92.5% of patients achieving at 80% PSA decline or greater by week 25 of therapy3. However, it is unknown if enzalutamide is more effective than bicalutamide in combination with standard ADT for patients with metastatic castration sensitive prostate cancer. 

    Published October 23, 2018
  • Imaging Controversies for Localized and Advanced Prostate Cancer

    Published in Everyday Urology - Oncology Insights: Volume 3, Issue 2
    Imaging in prostate cancer (PC) remains a controversial topic that can be challenging to navigate. In this article, I focus on some of the best tools in our current armamentarium: multiparametric prostate magnetic resonance imaging (mpMRI) for local prostate cancer (PC) and positron emission tomography-computed tomography (PET/CT) for advanced disease. In research settings, these modalities often overlap, but here I take a more practical approach by focusing on the use of PET/CT for the detection of metastatic disease.
    Published September 26, 2018
  • Patient Preferences for Metastatic Hormone-Sensitive Prostate Cancer Treatments: A Discrete Choice Experiment Among Men in Three European Countries.

    Various treatment options are available for metastatic hormone-sensitive prostate cancer. This study aimed to quantify how men with prostate cancer in the United Kingdom (UK), Germany, and Spain perceive the risks and benefits of hypothetical abiraterone acetate plus prednisone treatment and docetaxel-based chemotherapy treatment options.

    Published January 10, 2019
  • Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis.

    Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC).

    To systematically review trials of prostate radiotherapy.

    Using a prospective framework (framework for adaptive meta-analysis [FAME]), we prespecified methods before any trial results were known.

    Published March 8, 2019
  • Time from definitive therapy to onset of metastatic disease predicts outcomes in men with metastatic hormone sensitive prostate cancer.

    Contemporary treatment for metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) plus abiraterone or docetaxel. While these intensified regimens have improved efficacy, they are also associated with increased cost and toxicities.

    Published March 5, 2019
  • Treatment Advances in Metastatic Hormone-Sensitive Prostate Cancer

    Metastatic hormone-sensitive prostate cancer (mHSPC) is the disease space whereby men have metastatic prostate cancer and have never received (ie. are sensitive to) androgen deprivation therapy (ADT). mHSPC previously constituted ~30% of prostate cancer cases 1, however, from 2004-2012 secondary to PSA testing, the estimate was ~5% of cases 2. Many experts in the field suggest that with decreased PSA screening over the last few years, as a result of the United States Preventative Services Task Force (USPSTF) Grade D recommendation for PSA screening (subsequently upgraded to C 3), that these estimates are likely to once again increase 4. Typically, these patients have been treated with ADT alone, at which point the clock begins ticking towards a castration-resistant time point and eventual mortality. Since 2015, we have seen several landmark trials published that have added therapies to ADT for these men, favorably impacting overall survival (OS). This article will discuss the effect of docetaxel and abiraterone therapy among men with mHSPC and review the subsequent literature following reporting of these trials.

    Docetaxel and mHSPC

    In 2015, the CHAARTED trial changed the landscape of treatment of men with mHSPC. This trial randomized 790 men with mHSPC to receive either ADT + docetaxel (75 mg/m2 every 3 weeks for six cycles) (ADT-DOCE) or ADT alone, with OS as an endpoint 5. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT-DOCE than with ADT alone (57.6 months vs. 44.0 months; HR 0.61; 95%CI 0.47-0.80). Furthermore, the median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the ADT-DOCE group, as compared with 11.7 months in the ADT-alone group (HR 0.61, 95%CI 0.51-0.72). This trial ushered into clinical practice ADT-DOCE as the standard of care for men with mHSPC.

    Following reporting of the USA led CHAARTED trial, the UK STAMPEDE trial reported their OS outcomes of ADT-DOCE vs ADT alone 6. STAMPEDE uses a multi-arm, multi-stage platform, recruiting men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term ADT. Patients were randomized 2:1:1:1 to standard of care (SOC; ADT alone), SOC + zoledronic acid (SOC + ZA), SOC + docetaxel (ADT-DOCE), or SOC with both zoledronic acid and docetaxel (SOC + ZA + Doc). There were 2,962 men randomized between 2005 and 2013, including 1,817 (61%) men with M+ disease, 448 (15%) with N+/X M0, and 697 (24%) men who were N0M0. Over a median follow-up of 43 months (IQR 30–60), there were 415 deaths in the control group, with a median OS of 71 months (IQR 32-not reached (NR)) for SOC, NR (IQR 32-NR) for SOC + ZA (HR 0.94, 95%CI 0.79–1.11), 81 months (41-NR) for ADT-DOCE (HR 0.78, 95%CI 0.66–0.93), and 76 months (IQR 39-NR) for SOC + ZA + Doc (HR 0.82, 95%CI 0.69–0.97). These results recapitulated the findings of CHAARTED, as well as noting that zoledronic acid did not show an OS improvement when added to ADT alone.

    The GETUG-AFU15 phase III RCT was a French initiative, also testing ADT-DOCE vs ADT alone 7. Among 385 patients over a median follow-up of 83.9 months, the median OS was 62.1 months (95%CI 49.5–73.7) for ADT-DOCE and 48.6 months (95% CI, 40.9–60.6) for ADT alone (HR 0.88, 95%CI 0.68–1.14), thus failing to find a significant OS advantage for the addition of ADT-DOCE. The authors also analyzed several subgroups, post-hoc survival analyses, finding no ADT-DOCE advantage for men with high-volume disease (HR 0.78, 95%CI 0.56–1.09), low-volume disease (HR 1.02, 95%CI 0.67–1.55), nor for those with de novo metastatic disease (HR 0.93, 95%CI 0.69–1.25).

    This year, the CHAARTED trial published an updated survival analysis: at a median follow-up 53.7 months, the HR for OS was 0.72 (95%CI 0.59-0.89) favoring docetaxel over ADT standard of care, a 28% risk reduction of death compared to 39% in the first analysis 8. In subset analyses, the benefit was observed across all subgroups with two notable exceptions. Specifically, patients with a low burden of disease (HR 1.04, 95%CI 0.7-1.55) or those who had prior local therapy (HR 0.97, 95%CI 0.58-1.56) did not seem to experience a benefit through the addition of docetaxel to standard ADT.

    Abiraterone and mHSPC

    For nearly two years, ADT-DOCE was SOC for men with mHSPC. However, in 2017, two large phase III RCTs reported outcomes combining ADT + abiraterone acetate + prednisone (ADT-ABI) in this population, adding additional therapeutic options to the clinical repertoire 9, 10. LATITUDE was an international trial evaluating ADT-ABI compared to ADT alone among men with high-risk mHSPC 9. High-risk was defined as meeting at least two of three criteria: (i) Gleason score ≥8, (ii) presence of ≥3 lesions on bone scan, or (iii) presence of measurable visceral lesions. Patients were randomized 1:1 to either ADT-ABI (1000 mg abiraterone acetate + 5mg prednisone daily) (n=597) or ADT + placebo (n=602). The co-primary endpoints were OS and radiographic progression-free survival (rPFS). Secondary endpoints included time to pain progression, PSA progression, next symptomatic skeletal event, chemotherapy, and subsequent prostate cancer therapy. Over a median follow-up of 30.4 months, patients treated with ADT-ABI had a 38% risk reduction of death (HR 0.62, 95%CI 0.51-0.76) compared to ADT + placebo. Median OS was not yet reached in the ADT-ABI arm, compared to 34.7 months in the ADT + placebo arm. There was also a 53% risk of reduction of radiographic progression or death for patients treated with ADT-ABI compared to ADT alone (HR 0.47, 95%CI 0.39-0.55). Additionally, there was a statistically significant improvement across all secondary endpoints for ADT-ABI:

    1. Time to PSA progression (HR 0.30, 95%CI 0.26-0.35)
    2. Time to pain progression (HR 0.70, 95%CI 0.58-0.83)
    3. Time to next symptomatic skeletal event (HR 0.70, 95%CI 0.54-0.92)
    4. Time to chemotherapy (HR 0.44, 95%CI 0.35-0.56)
    5. Time to subsequent prostate cancer therapy (HR 0.42, 95%CI 0.35-0.50)

    Reporting at the same time as LATITUDE was the STAMPEDE abiraterone acetate arm 10. Inclusion criteria for the STAMPEDE ABI study included men with locally advanced or metastatic prostate cancer, including newly diagnosed with N1 or M1 disease, or any two of the following: stage T3/4, PSA ≥ 40 ng/mL, or Gleason score 8-10. Patients undergoing prior radical prostatectomy or RT were eligible if they had more than one of the following: PSA ≥ 4 ng/mL and PSADT < 6 months, PSA ≥ 20 ng/mL, N1, or M1 disease. These patients were then randomized 1:1 to SOC (ADT for ≥2 years, n=957) vs ADT-ABI (1000 mg abiraterone acetate + prednisone 5 mg daily, n=960). Treatment with RT was mandated in patients with N0M0 disease, while strongly encouraged for N1M0 patients. Primary outcomes were OS and failure-free survival (FFS), where failure was defined as PSA failure, local failure, lymph node failure, distant metastases or prostate cancer death. Over a median follow-up of 40 months, there was a 37% relative improvement in OS (HR 0.63, 95%CI 0.52-0.76) favoring ADT-ABI. Furthermore, ADT-ABI demonstrated a 71% improvement in FFS (HR 0.29, 95%CI 0.25-0.34) as well as significantly decreasing SREs among the entire cohort (HR 0.46, 95%CI 0.37-0.58) and specifically in the M1 cohort (HR 0.45, 95%CI 0.37-0.58).

    Based on the interim analysis findings of LATITUDE, the study was unblinded at the time of the first interim analysis. At the ASCO 2018 annual meeting, Dr. Fizazi presented longer-term efficacy analyses from this phase III trial 11. Median follow-up at the time of the second analysis was 41.0 months (range 0.1-54.0), 10.6 months longer than the initial analysis. There were 205 patients (34%) in the ADT-ABI arm and 70 patients (12%) in the ADT + placebo arm (of whom 57 patients (81%) had crossed over to ADT-ABI) who remained on treatment. Importantly, updated OS results continued to favor ADT-ABI compared to ADT alone (NR vs 36.7 months; HR 0.638, 95%CI 0.538-0.758). The results of the secondary endpoints also continued to favor ADT-ABI: (i) time to pain progression: 47.4 vs. 17. 9 months; HR 0.723, 95%CI 0.608-0.860; (ii) time to SRE: NR vs NR; HR 0.739, 95%CI 0.579-0.942; (iii) time to chemotherapy initiation: NR vs 47.3 months; HR 0.471, 95%CI 0.378-0.586; (iv) time to subsequent prostate cancer therapy: NR vs 21.2 months; HR 0.428, 95%CI 0.361-0.507.

    Comparing Docetaxel and Abiraterone

    Given the STAMPEDE design, recruitment of patients for the comparison of ADT-DOCE versus ADT alone overlapped for 16 months with recruiting patients for ADT-ABI + versus ADT alone 12. This design allowed for a comparison of randomized patients receiving ADT-DOCE to those receiving ADT-ABI. Stratified randomization allocated patients 2:1:2 to ADT alone, or ADT-DOCE, or ADT-ABI. There were 566 patients randomized to ADT-DOCE (n=189) and ADT-ABI (n=377). At a median follow up 4 years, the OS HR was 1.16 (95%CI 0.82-1.65; insignificantly favoring ADT-DOCE), FFS HR was 0.51 (95%CI 0.39-0.67; significantly favoring ADT-ABI), PFS HR was 0.65 (95%CI 0.48-0.88; significantly favoring ADT-ABI), MFS HR was 0.77 (95%CI 0.57-1.03; insignificantly favoring ADT-ABI), and SRE survival HR was 0.83 (95%CI 0.55-1.25; insignificantly favoring ADT-ABI).

    A second study used network meta-analysis methodology whereby an indirect comparison of two or more therapeutic options is possible through a common comparator arm. Wallis et al. 13 compared ADT-DOCE to ADT-ABI using data from GETUG, CHAARTED, LATITUDE, and the STAMPEDE trials. Overall, 6,067 patients were included: 1,181 (19.5%) patients who received ADT-DOCE, 1,557 (25.7%) patients who received ADT-ABI, and 3,329 (54.9%) patients who received ADT alone. The pooled HR for OS was 0.75 (95%CI 0.63–0.91) for ADT-DOCE versus ADT alone and 0.63 (95%CI 0.55–0.72) for ADT-ABI versus ADT alone. The indirect comparison of ADT-ABI to ADT-DOCE demonstrated no statistically significant difference in OS between treatments (HR 0.84, 95%CI 0.67– 1.06), and the findings were similar among patients with metastatic disease. Despite the lack of statistical significance, Surface Under the Cumulative Ranking Analysis (SUCRA) reported an 89% probability that ADT-ABI was the preferred first-line treatment option. Taken together, these studies suggest that although there is a trend favoring ADT-ABI for several outcomes, as the data currently stands, both ADT-ABI and ADT-DOCE are acceptable options for men with mHSPC.

    Patient Reported Outcomes

    Given that both ADT-ABI and ADT-DOCE improve OS outcomes, it becomes important to assess the impact on quality of life (QoL) metrics. A recently published analysis of the LATITUDE data assessing patient reported outcomes showed that patients receiving ADT-ABI had improved outcomes 14. The median time to worst pain intensity progression assessed by the BPI-SF score was not reached in either the ADT-ABI group (NR, 95%CI NR-NR; 25th percentile 11.1 months, 95%CI 9.22-18.4) or ADT group (NR, 95%CI NR-NR; 25th percentile 5.6 months, 95%CI 4.63-7.39), however with an HR of 0.63 (95%CI 0.52-0.77) favoring ADT-ABI. Similar findings were reported for median time to worst fatigue intensity (HR 0.65, 95%CI 0.53-0.81). Finally, the median time to deterioration of functional status assessed by the FACT-P total score scale was 12.9 months (95%CI 9.0-16.6) in the ADT-ABI group versus 8.3 months (7.4-11.1) in the ADT alone group (HR 0.85, 95%CI 0.74-0.99).

    Similarly, QoL data from the CHAARTED trial has also recently been published 15. Among the 790 men randomized, 90% completed FACT-P at baseline, 86% at 3 months, 83% at 6 months, 78% at 9 months, and 77% at 12 months. ADT-DOCE patients reported a statistically significant decline in FACT-P at 3 months (p < 0.001) but FACT-P did not differ significantly between baseline and 12 months (p = 0.38). ADT-DOCE FACT-P scores were significantly lower at 3 months (p = .02) but significantly higher at 12 months (p = .04) when compared with ADT alone FACT-P scores. Furthermore, ADT-DOCE patients reported significantly lower Functional Assessment of Chronic Illness Therapy-Fatigue scores at 3 months than ADT alone patients (p < .001).

    At this year’s GU ASCO meeting, Feyerabend et al. 16 presented results of an indirect treatment comparison of ADT-ABI and ADT-DOCE on patient-reported outcomes among men with mHSPC. The mean change from baseline was based on differences in FACT-P and BPI scores between active vs control arms in LATITUDE 9 (intention-to-treat ITT population) and CHAARTED 5. The probability of ADT-ABI being superior to ADT-DOCE at 3, 6, 9, and 12 months after treatment was based on fixed-effects Bayesian network meta-analysis. The authors found that the benefit in patient-reported outcomes with ADT-ABI vs ADT-DOCE was seen at 3 months and sustained for at least 1 year after treatment. This was consistent at each time point and for both FACT-P and BPI tools. The Bayesian probability of ADT-ABI being the better treatment for patient-reported outcomes ranged from 92.3% to 100%, with higher probabilities noted earlier in follow-up.

    Future Directions

    Cost Effectiveness

    There are significant cost differences when considering docetaxel or abiraterone. For example, for 100 patients with mHSPC, six cycles of upfront docetaxel (including visits, infusion, and cost of the drug) would cost $10,000 per patient. By subsequently adding abiraterone for an eventual rising PSA associated with CRPC ($8,000/month USD; with a median time to progression to CRPC of 18 months), this would cost $144,000 per patient ($15 million to treat 100 patients) with upfront docetaxel. For upfront abiraterone, at a median time to progression of 36 months (at $8,000/month USD) + $10,000 for post-abiraterone docetaxel, the total cost would be $30 million to treat 100 patients. Experts have suggested that there are several additional reasons to use docetaxel prior to abiraterone: (i) completed in 18 weeks with short term adverse events; (ii) docetaxel utilized earlier in the disease process allows chemotherapy treatment before the patient becomes too frail.

    Dr. Nicholas James and colleagues recently reported results of their analysis from STAMPEDE assessing whether adding docetaxel to the standard of care represents a cost-effective use of healthcare resources in M0 and M1 prostate cancer patients 17. Health outcomes and costs in the UK NHS were modeled using EuroQol (EQ-5D) and resource use data collected within the STAMPEDE trial. Lifetime predictions of costs, changes in predicted survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Compared to patients allocated standard of care, docetaxel was estimated to extend predicted survival by an average of 0.89 years for M1 patients and 0.78 years for M0 patients. Docetaxel was estimated to extend discounted QALYs by 0.51 years in M1 patients and 0.39 years in M0 patients. QALY gains in M0 patients were driven by the beneficial effect of delayed and reduced relapse – ie. patients receiving docetaxel spend more time in the hormone-sensitive state without treatment failure and less time with CRPC. Docetaxel was cost-effective both in M1 patients (ICER = £5,514/QALY vs. standard of care) and M0 patients (higher QALYs, lower costs vs. standard of care). The authors concluded that the probabilistic sensitivity analysis indicated a very high probability (> 99%) that docetaxel is cost-effective in both M0 and M1 patients.

    Subsequent Therapy

    Since CHAARTED was published nearly four years ago, data regarding subsequent therapy among patients initially receiving ABI-DOCE during the mHSPC disease state are emerging. Among 136 patients treated with upfront ABI-DOCE included in a multi-institutional study, the median time to CRPC was 19.6 months (IQR 16.6-22.6) 18. Sixty patients (44%) received ≥1 treatment for CRPC, including 48 patients (80%) receiving a second-generation hormonal therapy. Among these patients, 22 received abiraterone acetate, 20 enzalutamide, and six a novel CYP-17 inhibitor on trial (ASN-001). Patients receiving a second-generation hormonal therapy as the first treatment for mCRPC had a median radiographic PFS of 9.0 months (95%CI 6.9-11.2) compared with 3.0 months (95%CI, 1.5-4.5) for patients who received a non-second-generation hormonal therapy (p = 0.024).

    A separate multi-institutional study assessed the efficacy of abiraterone acetate vs enzalutamide in the mCRPC setting stratified by utilization of ADT-DOCE vs ADT alone in the mHSPC setting 19. Among 102 patients with mCRPC, 50 (49%) had previously received ADT alone, while 52 (51%) had ADT-DOCE. No statistically significant difference in any of the evaluated outcomes was observed between the two cohorts, however, deaths in the ADT-DOCE group were 12 compared to 21 in the ADT alone, after a median follow-up of 24.4 and 29.8 months, respectively.

    Ongoing Trials

    One of the most anticipated trials currently ongoing is the PEACE-1 phase III trial (NCT01957436) assessing SOC (ADT +/- docetaxel) vs SOC + abiraterone + prednisone vs SOC + local radiotherapy vs SOC + local radiotherapy + abiraterone + prednisone for men with de novo M1 prostate cancer. The co-primary outcomes are overall and progression-free survival. This trial has a target accrual of 1,168 patients, with more than 80% of patients already recruited. This trial will ultimately test whether ADT + abiraterone + docetaxel is even better than ADT-ABI or ADT-DOCE.


    Results of several large phase III RCTs over the past four years have improved survival and quality of life outcomes among men with mHSPC. Both docetaxel and abiraterone acetate in combination with ADT is the standard of care for patients in this disease state. Results of clinical trials assessing additional combinatorial therapy (ie. PEACE-1) are eagerly anticipated as we continue to strive for improved survival among prostate cancer patients with aggressive hormone-sensitive disease.
    Written by: Zachary Klaassen, MD, MSc
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    Published April 16, 2019

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