A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer.
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ABSTRACT: Background
Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone-sensitive prostate cancer (mHSPC). Real-world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC.Methods
In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression-free survival 1 (PFS1), and progression-free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. The Cox-proportional hazards model was used for univariate and multivariate regression analyses.Results
Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log-rank testing (23 vs. 13 mos., p < 0.001), a longer PFS2 (48 vs. 33 mos., p = 0.006), and longer OS (80 vs. 61 mos., p = 0.040). In the multivariate analyses AA+ADT outperformed D+ADT in terms of PFS1 (HR = 0.34, 95% CI = 0.183-0.623; p = 0.001) and PFS2 (HR = 0.33 95% CI = 0.128-0.827; p = 0.018), respectively, while OS and toxicity rate were similar between both groups.Conclusions
AA+ADT is mainly associated with a similar efficacy and overall toxicity rate as D+ADT. Further prospective research is required for validation of the clinical value of the observed benefit of AA+ADT for progression-free end-points.
SUBMITTER: Tsaur I
PROVIDER: S-EPMC8446402 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeProstate cancer is the second leading cause of cancer death in men in the US. Since 2015, landmark studies have demonstrated improved survival outcomes with the use of docetaxel (DCT) or abiraterone (AA) in addition to androgen deprivation therapy (ADT) in the metastatic hormone-naïve setting. These treatment strategies have not been prospectively compared but have similar overall survival benefits despite differing mechanisms of action, toxicity, and cost. We performed a cost-effectiveness analysis to provide insight into the value of AA vs. DCT in the first-line treatment of metastatic prostate cancer.Materials and methodsWe developed Markov models by using a US-payer perspective and a 3-year time horizon to estimate costs (2018 US$) and progression-free quality-adjusted life years (PF-QALYs) for ADT alone, DCT, and AA. Health states were defined as initial state, treatment states according to experience of an adverse event, and progressed disease/death. State transition probabilities were derived from rates for drug discontinuation, frequency of adverse events, disease progression, and death from the randomized phase III trials ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) and LATITUDE. Univariate and probabilistic sensitivity analyses were conducted to evaluate model uncertainty.ResultsDCT resulted in an increase of 0.32 PF-QALYs and $16,100 in cost and AA resulted in an increase of 0.52 PF-QALYs and $215,800 in cost compared to ADT alone. The incremental cost-effectiveness ratio for DCT vs. ADT was $50,500/PF-QALY and for AA vs. DCT was $1,010,000/PF-QALY. Probabilistic sensitivity analysis demonstrated that at a willingness-to-pay threshold of $150,000/PF-QALY AA was highly unlikely to be cost-effective.ConclusionDCT is substantially more cost-effective than AA in the treatment of metastatic hormone naïve prostate cancer.
| S-EPMC7751618 | biostudies-literature
Project description:More than a million men worldwide are diagnosed with prostate cancer every year. After androgen deprivation therapy (ADT), chemotherapy has been the only subsequent intervention to improve survival in the metastatic setting but has limitations for patients who may not tolerate its toxicity profile or are not candidates on the basis of comorbidities. Novel anti-androgens such as abiraterone acetate have shown promise for such patients. This review draws on clinical evidence and experience to identify abiraterone as a well-tolerated, effective alternative to docetaxel. In the castration-resistant setting, studies demonstrated a survival benefit over placebo, prompting further trials in the hormone-naïve population. More recently the STAMPEDE and LATITUDE studies suggest abiraterone has comparable survival outcomes to docetaxel in the castration-sensitive setting, with evidence in favour of its quality of life profile. Available comparisons with docetaxel are limited, but those available suggest they have comparable efficacy. However, the significant cost compared with docetaxel is a major barrier in resource-rationed healthcare settings. Overall, abiraterone is an effective alternative to chemotherapy for men with castration-sensitive prostate cancer, but this should be balanced with the significantly greater cost.
| S-EPMC6329025 | biostudies-literature
Project description:BackgroundAnemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC.MethodsWe retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019).ResultsWe found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia.ConclusionPretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.
| S-EPMC8152305 | biostudies-literature
Project description:BackgroundCurrently, metastatic hormone-sensitive prostate cancer (mHSPC) patients are often treated with docetaxel chemotherapy at the initiation of hormonal therapy. This treatment is based on the results of two pivotal trials. However, trial populations are not a representative of real-world patient populations.ObjectiveWe aimed to analyze whether survival rates in our daily practice cohort is comparable with those in clinical trials and to characterize the tolerability of docetaxel chemotherapy in daily practice.Design setting and participantsIn this retrospective cohort analysis, we studied 159 mHSPC patients treated with early docetaxel from April 2014 up to June 2020 in a top clinical hospital in The Netherlands. Patients were selected using hospital pharmacy records.Outcome measurements and statistical analysisWe compared the results of our cohort with the results of the cohorts of the two pivotal trials. We aimed to analyze the survival rates in our cohort and characterize the tolerability of docetaxel chemotherapy in daily practice.Results and limitationsDespite the relatively high number of comorbidities in our daily practice cohort, overall survival of our cohort showed great similarity with that of the two pivotal trials: 60.2 mo compared with 57.6 and 59.1 mo. Furthermore, early docetaxel was well tolerated in daily practice. Nearly 90% of the patients completed the full six cycles, and polyneuropathy led to relatively few dose reductions (6.9%).ConclusionsEarly docetaxel is well tolerated in daily practice. Our daily practice cohort showed great similarity in overall survival to the clinical trials. Our results might be of interest in the developing landscape of mHSPC treatment.Patient summaryWe studied docetaxel chemotherapy for metastatic prostate cancer in daily practice. These patients have the same survival as selected patients participating in clinical trials. Docetaxel was well tolerated in daily practice.
| S-EPMC8546919 | biostudies-literature
Project description:Importance:Men with metastatic prostate cancer who have a poor response to initial androgen-deprivation therapy (ADT), as reflected by a prostate-specific antigen (PSA) level higher than 4.0 ng/mL after 7 months of ADT, have a poor prognosis, based on historical controls. Objective:To determine the efficacy of abiraterone acetate with prednisone in these high-risk patients with a suboptimal response to hormonal induction. Design, Setting, and Participants:A phase 2 single-arm study was conducted through the National Clinical Trials Network-Southwest Oncology Group. Eligible patients had metastatic prostate cancer and a PSA level higher than 4.0 ng/mL between 6 and 12 months after starting ADT. The PSA level could be rising or falling at the time of enrollment, but had to be higher than 4.0 ng/mL. No previous chemotherapy or secondary hormonal therapies were allowed, except in patients receiving a standard, first-generation antiandrogen agent with a falling PSA level at the time of enrollment; this therapy was continued in this cohort. Abiraterone acetate, 1000 mg, once daily with prednisone, 5 mg, twice daily was administered to all participants. A total of 41 men were enrolled between the trial's activation on August 9, 2011, and closure on August 1, 2013. Data analysis was conducted from March 21 to November 29, 2016. Interventions:Abiraterone acetate, 1000 mg, once daily by mouth with prednisone, 5 mg, by mouth twice daily. Main Outcomes and Measures:The primary end point was a PSA level of 0.2 ng/mL or lower within 12 months of starting abiraterone acetate plus prednisone. A partial response (PR) was a secondary end point, defined as a PSA level reduction to lower than 4.0 ng/mL but higher than 0.2 ng/mL. Results:Of the 41 men enrolled, 1 did not receive any protocol treatment and was excluded from analysis. The median (range) age of the 40 participants was 66 (39-85) years. Five (13%) patients achieved a PSA level of 0.2 ng/mL or lower (95% CI, 4%-27%). Thirteen (33%) additional patients achieved a partial response, with a reduction in the PSA level to lower than 4.0 ng/mL but higher than 0.2 ng/mL. Sixteen (40%) patients had no PSA response and 6 (15%) were not assessable and assumed to be nonresponders. The median progression-free survival was 17.5 months (95% CI, 8.6-25.0 months) and the median overall survival was 25.8 months (95% CI, 15.7-25.8 months). There was 1 incident each of grade 4 adverse events of alanine aminotransferase level elevation and rectal hemorrhage. Eleven patients reported grade 3 adverse events. Conclusions and Relevance:This study did not reach its prescribed level of 6 PSA responses of 0.2 ng/mL or lower, although 5 responses were observed. The overall survival and progression-free survival rates observed in this trial are encouraging compared with historical controls. The therapy was generally well tolerated, without any clear signal of any unexpected adverse effects.
| S-EPMC5824213 | biostudies-literature
Project description:BackgroundMost men who die of prostate cancer are older than 70 years. The ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) randomized men of all ages with metastatic hormone-sensitive prostate cancer (mHSPC) to receive androgen deprivation therapy (ADT) with or without docetaxel demonstrating an overall survival (OS) benefit for docetaxel.MethodsIn a post-hoc analysis of this trial, we assessed patient characteristics and OS in patients ≥70 years ("older men") versus <70 years ("younger men") with Cox proportional hazards models. In addition, we compared adverse events, therapy completion rate, and subsequent treatment patterns between these two groups using Chi-squared tests.Results177 (22.4%) patients were ≥70 years. Docetaxel + ADT resulted in improved OS in both older and younger men (Hazard Ratio [HR] 0.45, 95%CI: 0.25-0.80 for older men; HR 0.71, 95%CI: 0.53-0.95 for younger men). This treatment benefit was seen for subgroups of older men with high volume disease (HR 0.43, 95%CI 0.23-0.79) and de novo metastatic disease (HR 0.36, 95%CI 0.19-0.69). A similar proportion of older and younger men completed six cycles of docetaxel (82.6% vs. 87.1%, p = 0.28). Rates of grade 3-5 adverse events were similar between older and younger men (36.8% vs. 26.8%, respectively, p = 0.069). The rate of any Grades 4-5 adverse events did not differ significantly between older and younger men (14.9% vs. 11.9%, respectively, p = 0.46). In the control arm, a smaller proportion of older men received subsequent cancer treatments (34.4% vs. 51.5%, p = 0.017) or subsequent docetaxel (25.6% vs. 37.6%, p = 0.035) compared to younger men.ConclusionsOlder men with mHSPC had similar OS benefit and clinical outcomes compared to younger men when receiving docetaxel + ADT. Oncologists should consider docetaxel chemotherapy as a favorable treatment option for older men with mHSPC who are fit for chemotherapy.
| S-EPMC8599519 | biostudies-literature
Project description:BackgroundAddition of docetaxel to androgen deprivation therapy (ADT) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been proved to be effective with an overall survival (OS) benefit in phase III clinical trials. The effectiveness of docetaxel with ADT in the general patient population remains unknown.ObjectiveThe purpose of this study is to report the clinical experience in mHSPC patients treated with 3rd-weekly docetaxel plus ADT in routine practice at two Danish institutions.Design setting and participantsA two-center retrospective study including consecutive mHSPC patients treated with 3rd-weekly docetaxel plus ADT was conducted.Outcome measurements and statistical analysisOutcomes of interest were OS, and biochemical and clinical progression-free survival.Results and limitationsA total of 173 consecutive patients with mHSPC who received docetaxel every 3rd week plus ADT between June 2015 and February 2018 were included. Most patients had high-volume disease (85%). All six planned docetaxel cycles were delivered in 149 cases (86%). Of the patients, 106 (61%) were alive at the last follow-up. At a median follow-up of 42 (37.8-58.6) mo, the median OS was 51.6 (41.5-56.3) mo. Castration-resistant prostate cancer (CRPC) developed in 46% within 1 yr, with a median time to CRPC of 15.6 (13.0-18.1) mo. Prostate-specific antigen nadir ≤0.2 ng/l was achieved in 15% of patients after 6 mo of ADT and in 19% after 12 mo.ConclusionsThe effect of docetaxel for mHSPC patients treated in routine practice appears comparable with the overall efficacy reported in the literature. Selection of patients will influence the results in clinical practice and clinical studies.Patient summaryIn this report, we looked at the clinical effectiveness of docetaxel combined with androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) in a Danish population. We found the effect of docetaxel treatment for mHSPC in the general population to be comparable with the overall efficacy reported in published studies.
| S-EPMC8317901 | biostudies-literature
Project description:ObjectivesTo evaluate the real-world data on the efficacy and safety of a combination therapy with radium-223 (Ra-223) and second-generation androgen-receptor targeting agents (ARTAs), including abiraterone acetate (ABI) and enzalutamide (ENZ), among Japanese patients with bone metastatic castration-resistant prostate cancer (CRPC).Patients and methodsWe retrospectively reviewed 79 patients with bone metastatic CRPC who were treated with Ra-223. The number of patients with concurrent ARTA use was 24:17 receiving ABI and 7 receiving ENZ. We evaluated the overall survival (OS) according to ARTA use and compared the survival of patients treated with Ra-223 with or without ARTA using multivariate analysis.ResultsThe median survival in the entire cohort was 23.5 months. The patients receiving Ra-223 combined with ARTA showed a tendency of better OS than patients treated with Ra-223 alone, although no significant difference was observed (median OS, 26.5 vs 23.5 months; P = .115). A multivariate analysis showed that the extent of disease on bone scan (EOD) scores and pain at baseline were significant predictors of OS. The concurrent use of bone-modifying agents (BMAs) was not significant for favorable OS (P = .050). However, the concurrent use of second-generation ARTA was not a significant factor for OS. Regarding safety, a bone fracture occurred in only one (4.2%) of 24 patients treated with combined Ra-223 and ARTA therapy.ConclusionOur real-world data analysis suggested that Ra-223 combined with a second-generation ARTA is well tolerated in Japanese patients. The EOD score and pain at baseline are significant prognostic factors for OS, but the concurrent use of second-generation ARTA has no influence on OS among men treated with Ra-223. The concurrent use of BMA yields a marginally favorable OS.
| S-EPMC8988769 | biostudies-literature
Project description:INTRODUCTION:This study aims to make an indirect comparison between enzalutamide and abiraterone acetate for mCRPC post-docetaxel. METHODS:A search for published phase 3 trials was performed with PubMed. Indirect comparisons of enzalutamide (AFFIRM) to abiraterone acetate (COU-AA-301) on outcomes overall survival (OS), time to prostate-specific-antigen (PSA) progression, radiographic progression-free survival (PFS), and PSA response were constructed in the context of log-linear regression models. RESULTS:There was no statistically significant difference in OS (hazard ratio (HR) 0.85, 95% CI 0.68-1.07). However, there was some evidence that enzalutamide may outperform abiraterone acetate with respect to secondary outcomes: time to PSA progression (HR 0.40, 95% CI 0.30-0.53), radiographic PFS (HR 0.61, 95% CI 0.50-0.74), and PSA response rates (RRs) (OR 10.69, 95% CI 3.92-29.20). CONCLUSION:While there was no statistically significant difference in OS, enzalutamide may be advantageous for secondary endpoints. Findings of this indirect comparison serve to be hypothesis-generating for future head-to-head trials.
| S-EPMC3964205 | biostudies-literature
Project description:BackgroundReal-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies.MethodsABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months. Several clinical and patients reported outcomes were examined.ResultsIn this second interim analysis, among 481 enrolled patients, 453 were evaluable for analyses. At baseline, the median age was 77 years and ~69% of patients had comorbidities (mainly cardiovascular diseases). Metastases were located mainly at bones and lymph nodes; 8.4% of patients had visceral metastases. During a median follow-up of 18 months, 1- and 2-year probability of radiographic progression-free survival were 73.9% and 56.2%, respectively; the corresponding rates for overall survival were 87.3% and 70.4%. In multivariable analyses, the number of bone metastases significantly affected radiographic progression-free survival and overall survival. During abiraterone plus prednisone treatment, 65% of patients had a ⩾50% prostate-specific antigen decline, and quality of life remained appreciably high. Among symptomatic patients according to the Brief Pain Inventory) (32%), scores significantly declined after 6 months of treatment. Overall, eight patients (1.7%) had serious adverse reactions to abiraterone.ConclusionsAbiraterone plus prednisone is effective and safe for chemotherapy-naïve mCRPC patients in clinical practice.
| S-EPMC7604981 | biostudies-literature