First-Line Treatment of Hormone-Sensitive Metastatic Prostate Cancer: Is There a Single Standard of Care?

2018 ◽  
Vol 36 (11) ◽  
pp. 1060-1061 ◽  
Author(s):  
Che-Kai Tsao ◽  
William K. Oh
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Standard Of Care ◽  
Line Treatment ◽  
First Line ◽  
Hormone Sensitive ◽  
Single Standard ◽  
First Line Treatment

scholarly journals A Cost-Effectiveness Analysis of Systemic Therapy for Metastatic Hormone-Sensitive Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Winnie W. Y. Sung ◽  
Horace C. W. Choi ◽  
Peter H. Y. Luk ◽  
Tsz Him So
Keyword(s):  
Prostate Cancer ◽  
Cost Effectiveness ◽  
Lifetime Cost ◽  
Treatment Options ◽  
Sensitivity Analyses ◽  
Line Treatment ◽  
First Line ◽  
Life Years ◽  
Hormone Sensitive ◽  
First Line Treatment

BackgroundCurrently, approved first-line treatment options of metastatic hormone-sensitive prostate cancer (mHSPC) include (1) androgen deprivation therapy (ADT) alone, ADT plus one of the following: (2) docetaxel, (3) abiraterone, (4) enzalutamide, and (5) apalutamide. The high cost of novel androgen receptor pathway inhibitors warrants an understanding of the combinations’ value by considering both efficacy and cost.ObjectiveThis study aimed to compare the cost-effectiveness of these five treatment options in mHSPC from the US payer perspective to guide treatment sequence.MethodsA Markov model was developed to compare the lifetime cost and effectiveness of these five first-line treatment options for mHSPC using outcomes data from published literature. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were obtained from the Veterans Affairs Pharmaceutical Catalog. We extrapolated survival beyond closure of the trials.Outcome Measurements and Statistical AnalysisLife-years, QALYs, lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. A willingness-to-pay (WTP) threshold of US$100,000 per QALY was used.ResultsCompared to ADT alone, docetaxel plus ADT provided a 0.28 QALY gain at an ICER of US$12,870 per QALY. Abiraterone plus ADT provided an additional 1.70 QALYs against docetaxel plus ADT, with an ICER of US$38,897 per QALY. Compared to abiraterone plus ADT, enzalutamide plus ADT provided an additional 0.87 QALYs at an ICER of US$509,813 per QALY. Apalutamide plus ADT was strongly dominated by enzalutamide plus ADT. Given the WTP threshold of US$100,000 per QALY, abiraterone plus ADT represented high-value health care.ConclusionsAbiraterone plus ADT is the preferred treatment option for men with mHSPC at a WTP threshold of US$100,000 per QALY.

Chemotherapy-Based Treatment for Castration-Resistant Prostate Cancer

2011 ◽  
Vol 29 (27) ◽  
pp. 3686-3694 ◽  
Author(s):  
Bostjan Seruga ◽  
Ian F. Tannock
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Cancer Trial ◽  
New Agents ◽  
Castration Resistant ◽  
First Line Treatment

Most men with metastatic prostate cancer respond to various types of androgen ablation but progress to castration-resistant disease. The TAX 327 and Southwest Oncology Group (SWOG) 99-16 clinical trials established docetaxel-based chemotherapy as preferred first-line treatment for most men with symptomatic metastatic castration-resistant prostate cancer (mCRPC). However, only about half receive benefit from docetaxel, and those who respond initially progress and eventually die of (or with) mCRPC. Both cellular mechanisms and the tumor microenvironment are implicated in the development of resistance to docetaxel. New agents are being evaluated for men with mCRPC, either as first-line treatment in combination with docetaxel, or in men progressing during or after treatment with docetaxel. Thus far, agents evaluated in phase III trials in combination with docetaxel have not improved outcome, including the vaccine GVAX, high-dose vitamin D (DN-101), and the antiangiogenic agent bevacizumab. In contrast, cabazitaxel, a taxane that is not cross-resistant to docetaxel, substantially improved the outcome of men progressing during or after treatment with docetaxel-based chemotherapy when compared with mitoxantrone and prednisone. However, translation of benefit of cabazitaxel demonstrated in the TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer) trial into general oncologic practice will be challenging because this agent may cause serious toxicity. With the approval of less toxic hormonal agents (eg, abiraterone acetate) in the setting of docetaxel-resistant mCRPC, clinicians will have an opportunity to balance benefits and harms of new agents in an individual patient and may be able to use different agents in sequence.

scholarly journals Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone-sensitive prostate cancer

2021 ◽  
Author(s):  
Miguel Gonzalez Velez ◽  
Heidi E. Kosiorek ◽  
Jan B. Egan ◽  
Andrea L. McNatty ◽  
Irbaz B. Riaz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Rank Test ◽  
Prognostic Impact ◽  
Line Treatment ◽  
First Line ◽  
Hormone Sensitive ◽  
First Line Treatment

Abstract Background Altered tumor suppressor genes (TSG-alt) in prostate cancer are associated with worse outcomes. The prognostic value of TSG-alt in metastatic, hormone-sensitive prostate cancer (M1-HSPC) is unknown. We evaluated the effects of TSG-alt on outcomes in M1-HSPC and their prognostic impact by first-line treatment. Methods We retrospectively identified patients with M1-HSPC at our institution treated with first-line androgen deprivation therapy plus docetaxel (ADT + D) or abiraterone acetate (ADT + A). TSG-alt was defined as any alteration in one or more TSG. The main outcomes were Kaplan–Meier-estimated progression-free survival (PFS) and overall survival, analyzed with the log-rank test. Clinical characteristics were compared with the χ2 test and Kruskal–Wallis rank sum test. Cox regression was used for univariate and multivariable analyses. Results We identified 97 patients with M1-HSPC: 48 (49%) with ADT + A and 49 (51%) with ADT + D. Of 96 patients with data available, 33 (34%) had 1 TSG-alt, 16 (17%) had 2 TSG-alt, and 2 (2%) had 3 TSG-alt. The most common alterations were in TP53 (36%) and PTEN (31%); 6% had RB1 alterations. Median PFS was 13.1 (95% CI, 10.3–26.0) months for patients with normal TSGs (TSG-normal) vs. 7.8 (95% CI, 5.8–10.5) months for TSG-alt (P = 0.005). Median PFS was lower for patients with TSG-alt vs TSG-normal for those with ADT + A (TSG-alt: 8.0 [95% CI, 5.8–13.8] months vs. TSG-normal: 23.2 [95% CI, 13.1–not estimated] months), but not with ADT + D (TSG-alt: 7.8 [95% CI, 5.7–12.9] months vs. TSG-normal: 9.5 [95% CI, 4.8–24.7] months). On multivariable analysis, only TSG-alt predicted worse PFS (hazard ratio, 2.37; 95% CI, 1.42–3.96; P < 0.001). Conclusions The presence of TSG-alt outperforms clinical criteria for predicting early progression during first-line treatment of M1-HSPC. ADT + A was less effective in patients with than without TSG-alt. Confirmation of these findings may establish the need for inclusion of molecular stratification in treatment algorithms.

Docetaxel, Vinorelbine, and Zoledronic Acid as First-Line Treatment in Patients with Hormone Refractory Prostate Cancer: A Phase II Study

2007 ◽  
Vol 52 (4) ◽  
pp. 1020-1027 ◽  
Author(s):  
Giuseppe Di Lorenzo ◽  
Riccardo Autorino ◽  
Sisto Perdonà ◽  
Michele De Laurentiis ◽  
Massimo D'Armiento ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Hormone Refractory Prostate Cancer ◽  
Line Treatment ◽  
First Line ◽  
Hormone Refractory ◽  
First Line Treatment

Combination Androgen Receptor Inhibition and Docetaxel in Metastatic Castration-sensitive Prostate Cancer: The Next Step in First-line Treatment?

2020 ◽  
Vol 18 (6) ◽  
pp. 425-428 ◽  
Author(s):  
Jacob J. Adashek ◽  
Jarred P. Reed ◽  
Ankita Tandon ◽  
Stephen J. Freedland ◽  
Edwin Posadas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Line Treatment ◽  
First Line ◽  
Receptor Inhibition ◽  
First Line Treatment

Weekly Docetaxel and Vinorelbine (VIN-DOX) as First Line Treatment in Patients with Hormone Refractory Prostate Cancer

2004 ◽  
Vol 46 (6) ◽  
pp. 712-716 ◽  
Author(s):  
Giuseppe Di Lorenzo ◽  
Carmine Pizza ◽  
Riccardo Autorino ◽  
Michele De Laurentiis ◽  
Ombretta Marano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormone Refractory Prostate Cancer ◽  
Line Treatment ◽  
First Line ◽  
Weekly Docetaxel ◽  
Hormone Refractory ◽  
First Line Treatment

scholarly journals Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application

2020 ◽  
Vol 11 ◽  
pp. 204201882095833
Author(s):  
Jan Längericht ◽  
Irene Krämer ◽  
George J. Kahaly
Keyword(s):  
Low Cost ◽  
Standard Of Care ◽  
Daily Basis ◽  
Clinical Severity ◽  
Line Treatment ◽  
First Line ◽  
Graves Orbitopathy ◽  
Meta Analyses ◽  
First Line Treatment

Background: Graves’ orbitopathy (GO) is the most frequent extrathyroidal manifestation of the autoimmune Graves’ disease. GO significantly impacts quality of life and has a psycho-social morbidity. Inflammation and swelling of the orbital tissue often leads to proptosis, diplopia, and decrease of visual acuity. Due to the inflammatory background of the disease, glucocorticoids (GC) have been used as a first-line treatment for decades. Methods: PubMed and MeSH database were searched for original articles, clinical trials, reviews, and meta-analyses published between 1 January 2000 and 31 March 2020 and pertaining to both the mechanism of action and immunological effects of GC as well as to the treatment of GO by GC. The publications were evaluated according to their setting and study design. Results: GC act through genomic (trans-activation and trans-repression) and rapid non-genomic mechanisms. GC in general, and the intravenous (IV) administration of GC in particular, markedly decrease the activity and number of the most potent antigen-presenting dendritic cells. According to the internationally acknowledged European Thyroid Association Guidelines for the management of GO, weekly IVGC application over 12 weeks is recommended as first-line treatment for patients with active and severe GO. The daily and cumulative dose should be tailored according to clinical severity, for example, 4.5 g of IV methylprednisolone for the inflammatory component versus 7.5 g in the presence of diplopia and severe proptosis. Fast and significant improvements in orbital symptoms and signs are noted in 65–70% of patients. Long-term experience over decades, and worldwide availability at low cost, underline the clinical and therapeutic relevance of GC. Adverse events are rarely severe, dose-dependent, and usually reversible, hence easy to handle by medical investigators. Oral GC application on a daily basis is characterized by high bioavailability but reduced efficacy and increased toxicity. Conclusion: IVGC still represents the standard of care in active/severe GO. Innovative biologicals, like monoclonal antibodies targeting the thyrotropin/Insulin-like growth factor-1 receptors or pro-inflammatory cytokines (e.g., Interleukin-6) should be compared with standard GC treatment with respect to short- and long-term efficacy, safety, costs, and global availability.

scholarly journals RADI-08. A SURVEY BASED STUDY OF BRAIN METASTASES MANAGEMENT FOR PATIENTS WITH NON-SMALL CELL LUNG CANCERS OR MELANOMA

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i23-i23
Author(s):  
Chin Heng Fong ◽  
Natasha Leighl ◽  
Marcus Butler ◽  
Mark Doherty ◽  
Timothy Kruser ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Kinase Inhibitors ◽  
Standard Of Care ◽  
Line Treatment ◽  
First Line ◽  
Exact Test ◽  
Lung Cancers ◽  
Radiation Oncologists ◽  
First Line Treatment

Abstract INTRODUCTION: The standard of care for 1–4 brain metastases (BrM) is stereotactic radiosurgery (SRS), whereas whole brain radiation remains the standard treatment for extensive BrM, and surgical resection is appropriate in certain scenarios. Some newer systemic therapies such as tyrosine kinase inhibitors and immunotherapy have impressive CNS activity and are used by some practitioners either alone or in combination with other modalities as first-line treatment for BrM. We conducted a survey to ascertain current real-world practices for the treatment of BrM from NSCLC and melanoma. OBJECTIVES: Our study aimed to assess practice patterns of oncologists who treat BrM from NSCLC or melanoma. We also investigated the extent to which various clinical factors influence decision making. METHODOLOGY: We created 2 sets of surveys: one for Medical-/Clinical-/Neuro- oncologists and another for Radiation oncologists/Neurosurgeons. Surveys were conducted online or on-line. Following administration, data was tabulated and analyzed. Statistical analyses were performed using Fisher’s exact test. RESULTS: Of 361 respondents, 250 were Radiation oncologists/Neurosurgeons, and 111 were Medical-/Clinical-/Neuro- oncologists. For patients with 1–3 brain lesions, all &lt; 2cm, 34% of respondents recommended systemic therapy alone as first-line treatment. In contrast, only 15% recommend systemic therapy alone for &gt;9 lesions, at least one &gt; 2cm. Medical-/Clinical-/Neuro- oncologists were more likely to recommend systemic therapy alone compared to Radiation oncologists/ Neurosurgeons for 1–3 lesions, all &lt; 2cm (53% vs. 28%, p&lt; .0001). For patients with &gt; 9 BrM, one &gt;2cm diameter, Medical-/Clinical-/Neuro- oncologists were not significantly more likely to recommend systemic therapy alone (20% vs 13%, p=.11). DISCUSSION: Our results reveal that significant numbers of physicians recommend systemic therapy alone as first-line therapy in BrM and that management decisions correlate with a physician’s type of practice. These findings underscore the need for prospective clinical trials to direct appropriate BrM management.

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