Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer: The Prostate Cancer Registry

Abstract

Background Metastatic prostate cancer has a 30% 5-year survival rate despite recent therapeutic advances. There is a need to improve the clinical understanding and treatment of this disease, particularly in the real-world setting and among patients who are under-represented in clinical trials. Objective We aimed to evaluate the characteristics and clinical outcomes of patients who received their first treatment for metastatic castration-resistant prostate cancer (mCRPC) in routine clinical practice, independent of treatment used, including subgroups with baseline cardiac disease, diabetes mellitus, or visceral metastases. Patients and methods Prospective, noninterventional analysis of patient record data in the multicenter Prostate Cancer Registry (PCR) of men with mCRPC. The data were collected in 16 countries with the aim of recruiting more than 3000 patients between 2013 and 2016. The study end date was 9 July 2018. Data evaluated included baseline characteristics, treatment exposure, and efficacy outcomes [overall survival (OS) and time to progression (TTP)] of patients treated with abiraterone acetate plus prednisone or prednisolone (collectively, "abiraterone"), enzalutamide, or docetaxel. Descriptive outcomes are reported from the overall patient population and subgroups of patients with baseline cardiovascular disease, diabetes mellitus, or visceral metastases. The treatment effects for time to progression were compared for the overall patient population. Results The study enrollment period lasted 2.5 years, and each patient was followed for a maximum of 3 years. A total of 1874 patients in the PCR had not received previous mCRPC treatment at baseline, although they had received androgendeprivation therapy. Prevalent co-morbidities included cardiovascular disease in 65.4% and diabetes mellitus in 17.4% of patients. Baseline characteristics suggested that patients with more advanced disease received docetaxel treatment. In the overall patient population, the median time to progression with abiraterone, enzalutamide, and docetaxel as first-line mCRPC therapy was 9.6, 10.3, and 7.6 months, respectively, and median OS was 27.1, 27.1, and 27.9 months, respectively. Outcomes in the subgroups of patients with cardiovascular disease or diabetes mellitus were similar to those of the whole population in the analysis. As expected, patients with visceral metastases had shorter TTP and OS than patients in the overall population. Conclusions This analysis shows, for the first time, the effectiveness in parallel of first-line abiraterone, enzalutamide, and docetaxel in mCRPC, including in patients with co-morbidities such as cardiovascular disease or diabetes mellitus or in patients with visceral metastases. These real-world findings from the PCR provide meaningful information to help manage mCRPC, particularly in patients under-represented in clinical studies. Trial Registration ClinicalTrials.gov identifier NCT02236637; registered September 2014.

Comparison of the oncological outcomes of abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer: A multicenter real-life data

“…Simon et al compared rst line AA, E and docetaxel activities in a multi-center, retrospective study of 1874 patients with mCRPC. The median time to progression in the AA, E and docetaxel groups was 9.6, 10.3, and 7.6 months, respectively; the median OS was 27.1, 27.1, and 27.9 months, respectively 11 . In our study, rPFS was 12 and 17 months in the AA and E groups, and the median OS was 24 and 29 months, respectively.…”

Treatment-Emergent Co-Morbidities and Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Abiraterone or Enzalutamide

“…The existing confounders of age, chemotherapy, hypertension, duration of follow-up, and duration of medication use were statistically significantly different in these two groups of patients. Furthermore, a causal relationship between these confounding factors and comorbidities has been well established-for example, between age and comorbidities (Piccirillo et al, 2008), age and overall survival (Piccirillo et al, 2008), hypertension and cerebrovascular accident (Meschia et al, 2014), chemotherapy and survival (Chowdhury et al, 2020), hypertension and life expectancy (Turin et al, 2012), and hypertension and cardiovascular disease (Francula-Zaninovic and Nola, 2018). We also used the duration of medication use to confirm the hypothesis that medication exposure time is correlated to accumulation of a comorbidity; this result has been observed in another study of patients receiving androgen deprivation therapy (O'Farrell et al, 2015).…”

A Retrospective Observational Analysis of Overall Survival with Sipuleucel-T in Medicare Beneficiaries Treated for Advanced Prostate Cancer

“…The men described in the current retrospective study started their first treatment in 2014 and were followed for 36 months. Other descriptions of treatment outcomes in contemporaneous populations of men with mCRPC have been published recently: the observational PROCEED safety registry conducted in the US and described by Higano et al [31], the analysis of electronic health records from US oncology practices curated by Flatiron and described by George et al [10], and the report of a prospective ex-US patient registry described by Chowdhury et al [38]. While not directly comparable, George et al [10] and Higano et al [31] may provide some clinical insight into the patients in the current study as they include contemporaneous and potentially overlapping populations.…”

“…Data from the current study and both Higano et al [31] and George et al [10], all from the US, exhibit similar outcomes, likely a reflection of how available treatment guidelines inform physician prescribing practices. In contrast, Chowdhury et al [38] describe treatment in Europe and other countries where sipuleucel-T is not available, and thus treatment guidelines differ. Furthermore, each study is represented by different types of data sources, each with their own set of research assumptions and biases.…”

“…After controlling for confounders such as baseline differences between groups by using a multivariable analysis, survival after sipuleucel-T treatment was significantly longer than that observed after ASPI treatment. Even given the potential limitations associated with claims analyses, such as selection bias and confounding by indication, this research provides important insights into real-world treatment outcomes and is complementary with other recently published real-world evidence analyses from other data sources [ 10 , 31 , 38 ]. In summary, this analysis provides important and hypothesis-generating information on the treatment of mCRPC that should be validated to contextualize these results for clinical application.…”