Treatment Intensification for Low-risk Metastatic Hormone-sensitive Prostate Cancer: The Time Is Now.
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ABSTRACT:
SUBMITTER: McKay RR
PROVIDER: S-EPMC9525807 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Treatment Intensification for Low-risk Metastatic Hormone-sensitive Prostate Cancer: The Time Is Now.
European urology open science 20220928
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Project description:The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has dramatically evolved. Monotherapy androgen deprivation therapy (ADT) with testosterone suppression alone is no longer the standard of care as multiple global phase 3 trials of different combinatorial strategies have been clinically and statistically successful and the combinations have been incorporated into guidelines on advanced prostate cancer. For appropriate patients, clinicians should consider combining ADT with docetaxel or an androgen receptor pathway inhibitor, or possibly with both. Shared patient-physician decision-making mandates a review of the level 1 evidence supporting the optimization and intensification of combination therapy for patients with mHSPC. Here we discuss the evidence underscoring intensification strategies as the standard of care for low-volume, low-risk mHSPC.Patient summaryWe discuss treatment strategies for men with metastatic prostate cancer. Combinations of androgen deprivation therapy (ADT) and drugs that inhibit the androgen receptor pathway are superior to ADT alone and prolong survival in patients with metastatic hormone-sensitive prostate cancer.
| S-EPMC9523347 | 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:The landscape of advanced prostate cancer treatment has evolved tremendously in past decades. The treatment paradigm has shifted from androgen deprivation therapy (ADT) alone to doublet combinations comprising ADT with docetaxel or an androgen receptor inhibitor, and now triplet therapy involving all 3 classes of agents. Robust clinical data has demonstrated survival benefits with this strategy of upfront treatment intensification. Subgroup analysis has alluded to the importance of tailoring treatment according to metastatic disease burden. However, defining the volume of disease is becoming increasingly controversial due to the advent of next generation molecular imaging. Several trials testing established agents in the castrate-resistant setting are now underway in metastatic hormone sensitive prostate cancer patients. As the treatment milieu is enriched earlier in the disease trajectory, future studies should elucidate biomarkers to further define specific patient populations who will benefit most from treatment intensification and/or de-escalation, with what agents and for what duration.
| S-EPMC10415497 | biostudies-literature
Project description:The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.
| S-EPMC8409413 | biostudies-literature
Project description:PURPOSE:To capture UK societal health utility values for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and the disutility associated with treatment-related adverse events (AEs) to inform future cost-utility analyses. METHODS:A literature review, and patient and clinical expert interviews informed the development of health states characterising mHSPC symptoms and the impact of treatment-related AEs on health-related quality of life (HRQL). Three base health states were developed describing a typical patient with high-risk mHSPC: receiving androgen deprivation therapy (ADT) [Base State 1]; receiving docetaxel plus ADT [Base State 2]; completed docetaxel and still receiving ADT whose disease has not yet progressed [Base State 3]. Six additional health states described treatment-related AEs. The health states were validated with experts and piloted with general public participants. Health state utilities were obtained using the time trade-off (TTO) method with 200 members of the UK general population. A generalised estimating equation (GEE) model was used to estimate disutility weights. RESULTS:Mean TTO scores for Base State 1 to 3 were 0.71 (SD?=?0.26), 0.64 (SD?=?0.27), and 0.68 (SD?=?0.26), respectively, indicating that receiving docetaxel plus ADT was most impactful on HRQL. The GEE model indicated when compared to Base State 2 that the nausea and vomiting AE had the most impact on HRQL (-?0.21), while alopecia was least burdensome (-?0.04). CONCLUSIONS:The study highlights the differences in utility between base health states and the significant impact of treatment-related AEs on the HRQL of patients with mHSPC. These findings underline the importance of accounting for impaired HRQL when assessing treatments for mHSPC.
| S-EPMC6470112 | biostudies-literature
Project description:BackgroundAndrogen-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.MethodsWe assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone.ResultsA total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%.ConclusionsSix cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.).
| S-EPMC4562797 | biostudies-literature
Project description:BACKGROUND:Currently, there is no universally accepted prognostic classification for patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT). Subgroup analyses demonstrated that pts with low volume (LV), per CHAARTED trial definition, mHSPC, and those who relapse after prior local therapy (PLT) have longer overall survival (OS) compared to high volume (HV) and de-novo (DN), respectively. Using a hospital-based registry, we aimed to assess whether a classification based on time of metastatic disease (PLT vs DN) and disease volume (LV vs HV) are prognostic for mHSPC pts treated with ADT. METHODS:A retrospective cohort of consecutive patients with mHSPC treated with ADT between 1990 and 2013 was selected from the prospectively collected Dana-Farber Cancer Institute database and categorized as DN or PLT and HV or LV, at time of ADT start. Primary and secondary endpoints were OS and time to castration-resistant prostate cancer (CRPC), respectively, which were measured from date of ADT start using Kaplan-Meier method. Multivariable Cox proportional hazards models using known prognostic factors was used. RESULTS:The analytical cohort consisted of 436 patients. The median OS and time to CRPC for PLT/LV were 92.4 (95%CI: 80.4-127.2) and 25.6 (95%CI: 21-35.7) months and 43.2 (95%CI: 37.2-56.4) and 12.2 (95%CI: 9.8-14.8) months for DN/HV, respectively, whereas intermediate values were observed for PLT/HV and DN/LV. A robust gradient for both outcomes was observed (Trend test P?<?0.0001) in the four groups. In a multivariable analysis, DN presentation, HV, and cancer-related pain were independent prognostic factors. CONCLUSIONS:In our hospital-based registry, time of metastatic presentation and disease volume were prognostic for mHSPC pts treated with ADT. This simple prognostic classification system can aid patient counseling and future trial design.
| S-EPMC6171350 | biostudies-literature
Project description:Prostate cancer continues to be one of the most commonly diagnosed cancers in men globally and a leading cause of male cancer deaths. The landscape of metastatic hormone-sensitive prostate cancer has significantly changed over the past decade. For many years, androgen deprivation therapy alone through surgical or chemical castration was the mainstay of treatment yielding limited 5-year survival rates. New treatment approaches using Docetaxel chemotherapy or androgen receptor pathway inhibitors to intensify upfront systemic therapy have resulted in significantly improved survival rates compared to androgen deprivation therapy alone. Clinicians are now equipped with an arsenal of drugs capable of prolonging life for metastatic hormone-sensitive prostate cancer patients. Furthermore, new treatment modalities are being tested in clinical trials making treatment of metastatic hormone-sensitive prostate cancer an extremely dynamic space. In this narrative review, we provide an overview of the key systemic treatments for metastatic hormone-sensitive prostate cancer, namely androgen deprivation therapy, novel androgen receptor pathway inhibitors and Docetaxel. We summarise a series of landmark trials that have led to the integration of novel androgen receptor pathway inhibitors and docetaxel into the treatment paradigm for metastatic hormone-sensitive prostate cancer. Lastly, we discuss nursing, financial and side-effect considerations pertaining to the use of these drugs. This article aims to give its readers an understanding of the evidence and clinical aspects of novel therapies in metastatic hormone-sensitive prostate cancer as they become increasingly available for use around the world.
| S-EPMC8575582 | biostudies-literature
Project description:BackgroundDarolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown.MethodsIn this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival.ResultsThe primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively).ConclusionsIn this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602.).
| S-EPMC9844551 | biostudies-literature
Project description:The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has changed radically in recent years. Androgen deprivation therapy (ADT) alone was for decades the standard of care for treating mHSPC. This changed when studies showed that the addition of docetaxel chemotherapy or abiraterone acetate to ADT significantly increases overall survival of patients with mHSPC, followed by more recent evidence showing the efficacy of androgen receptor antagonists, such as enzalutamide and apalutamide, in this setting. While this rapid therapeutic evolution is welcome, it presents clinicians with a crucial challenge: the choice of treatment selection and sequencing. In the first-line setting there are no comparative data currently available to guide treatment choice between the different available regimens, and no prospective data to guide clinical decision after progression. Decisions on treatment will now need to be personalised based on indirect comparison of the available efficacy data from multiple phase 3 studies, together with considerations of disease volume, comorbidities, treatment aims, toxicity profile and cost reimbursement within the healthcare setting. Here, we provide an overview of the clinical trial data to date and propose some biological and clinical insights which may be helpful in making decisions on treatment selection and sequencing.
| S-EPMC7683690 | biostudies-literature