scholarly journals Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4522
Author(s):  
Carlo Cattrini ◽  
Rodrigo España ◽  
Alessia Mennitto ◽  
Melissa Bersanelli ◽  
Elena Castro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Predictive Biomarkers ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Resistant Disease ◽  
Castration Resistant ◽  
Optimal Sequencing ◽  
Radium 223 ◽  
Signaling Inhibitors

The treatment landscape of advanced prostate cancer has completely changed during the last decades. Chemotherapy (docetaxel, cabazitaxel), androgen-receptor signaling inhibitors (ARSi) (abiraterone acetate, enzalutamide), and radium-223 have revolutionized the management of metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177–PSMA-617 is also going to become another treatment option for these patients. In addition, docetaxel, abiraterone acetate, apalutamide, enzalutamide, and radiotherapy to primary tumor have demonstrated the ability to significantly prolong the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Finally, apalutamide, enzalutamide, and darolutamide have recently provided impactful data in patients with nonmetastatic castration-resistant disease (nmCRPC). However, which is the best treatment sequence for patients with advanced prostate cancer? This comprehensive review aims at discussing the available literature data to identify the optimal sequencing approaches in patients with prostate cancer at different disease stages. Our work also highlights the potential impact of predictive biomarkers in treatment sequencing and exploring the role of specific agents (i.e., olaparib, rucaparib, talazoparib, niraparib, and ipatasertib) in biomarker-selected populations of patients with prostate cancer (i.e., those harboring alterations in DNA damage and response genes or PTEN).

Management of Castration-resistant Prostate Cancer: Second-line Therapies

2018 ◽  
Author(s):  
Samer L Traboulsi ◽  
Fred Saad
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Key Words ◽  
Abiraterone Acetate ◽  
Line Treatment ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Optimal Sequencing ◽  
Radium 223

Until 2010, the only approved life-prolonging treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) was docetaxel. Since 2010, abiraterone acetate, enzalutamide, and cabazitaxel have demonstrated overall survival (OS) benefits in the postdocetaxel setting. The COU-AA-301 trial showed an OS advantage with abiraterone acetate plus prednisone compared with placebo plus prednisone. A superior OS was also seen in the AFFIRM trial that compared enzalutamide with placebo and in the TROPIC trial that compared cabazitaxel plus prednisone with mitoxantrone plus prednisone Radium-223 dichloride has also been approved based on the ALSYMPCA trial for symptomatic patients with castration-resistant prostate cancer (CRPC) metastatic to bone only. Optimal sequencing of approved therapies remains controversial. In this chapter, we will review the approved agents in second-line treatment of CRPC and discuss the sequencing options. This review contains 4 figures, 5 tables, and 57 references. Key Words: abiraterone acetate, cabazitaxel, castration-resistant, docetaxel, enzalutamide, MDV 3100, prostatic neoplasms, radium-223 dichloride, sequencing of therapy

scholarly journals CLINICAL CASE OF A PATIENT UNDERGOING RADIUM-223 TREATMENT FOLLOWING TREATMENT WITH ABIRATERONE ACETATE AND ENZALUTAMIDE

2018 ◽  
Vol 40 (2) ◽  
pp. 144-148 ◽  
Author(s):  
M E Jimenez Romero ◽  
S Diez Farto ◽  
J C Navarro Serrato ◽  
E Canelon Castillo ◽  
I Revelo Cadena
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Predictive Biomarkers ◽  
Sequential Therapy ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Genetic Characteristics ◽  
Prior Therapy ◽  
Castration Resistant ◽  
Radium 223

Objective: Over the last decade, significant advances have been made in the development of therapies for patients with metastatic castration-resistant prostate cancer. Abiraterone and enzalutamide were approved as treatments based on data supporting improved overall survival compared to placebo. Radium-223 became the first approved radiopharmaceutical which decreased skeletal-related events, palliated pain, and showed improved overall survival in symptomatic patients with castration-resistant prostate cancer and bone metastasis only. Materials and Methods: We present the case of an eighty-two year old man with metastatic castrationresistant prostate cancer who was treated with sequential therapy (abiraterone — enzalutamide — radium 223). The sequencing and treatment used for our patient was viable because of his clinical characteristics, which have allowed for longer survival time with an acceptable quality of life. These actions must be agreed on by the Multidisciplinary Tumour Board, in order to optimize the use of available courses of treatment. Results: The treatment of these patients is changing rapidly, but many questions remain regarding the optimal sequencing of the available drugs. Sequential or concomitant use of the next generation hormonal agents — abiraterone and enzalutamide — cannot currently be recommended. Data regarding the safety of concomitant abiraterone, enzalutamide or denosumab with radium-223 is reassuring and timely. However, we cannot advocate the general use of combined radium-223 therapy at this time, irrespective of prior therapy. Conclusion: A better understanding of active mechanisms, the genetic characteristics of each metastatic castration-resistant prostate cancer and the development of new prognostic and predictive biomarkers will help determine sequencing or different combination treatments for each individual patient.

Novel therapies and emerging strategies for the treatment of patients with castration-resistant prostate cancer

2017 ◽  
Author(s):  
Deborah Mukherji ◽  
Aurelius Omlin ◽  
Carmel Pezaro ◽  
Johann De Bono
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Trial Participation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
New Treatments ◽  
Phase Iii Studies ◽  
Clinical And Translational Research

Castration-resistant prostate cancer (CRPC) represents a final stage of this malignancy for many men and is defined as the progression of prostate cancer despite castrate levels of testosterone. CRPC may present as a rising PSA, the development of new metastases, or worsening of known metastases. Recent advances have resulted in five new treatments for CRPC: the immunotherapy sipuleucel-T; the cytotoxic cabazitaxel; the androgen biosynthesis inhibitor abiraterone acetate; the radioisotope radium-223; and the antiandrogen enzalutamide. These have all improved overall survival in randomized phase III studies for patients with metastatic CRPC. Furthermore, multiple agents and combinations are currently in late-stage clinical testing. Men with advanced prostate cancer represent an important population for clinical and translational research and clinical trial participation should be considered as part of standard care.

scholarly journals The Potential for Chemotherapy-Free Strategies in Advanced Prostate Cancer

2019 ◽  
Vol 13 (2) ◽  
pp. 57-63 ◽  
Author(s):  
Bulent Cetin ◽  
Ahmet Ozet
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Short Communication ◽  
Unmet Needs ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
New Agents ◽  
Chemotherapy Drugs ◽  
Optimal Sequencing ◽  
Radium 223

The treatment landscape for advanced prostate cancer is evolving rapidly, with new agents and strategies, and more optimal use of existing therapies under constant development. Efforts were focused on better understanding of the biology of the disease.This effort has paved the way for a more contemporary and effective therapies to be developed. There are now 6 FDA-approved therapies that increase overall survival. These include the immunotherapy sipuleucel-T; the 2 androgen pathway inhibitors: abiraterone acetate and enzalutamide; 2 chemotherapy drugs: docetaxel and cabazitaxel; and the radionuclide: radium-223. Advanced prostate cancer may be one of the few cancers for which multiple chemotherapy and nonchemotherapy regimens are considered as standard. Several recently published clinical trials have demonstrated the suprising activity of chemotherapy-free strategies, and we should not be too eager to discount these ‘‘old-fashioned'' treatments. Optimal sequencing is still unclear because new therapies have proliferated so quickly that comparative data are limited. In this short communication, we identify current challenges and unmet needs in advanced prostate cancer and provide an overview of their respective clinical activity, while highlighting distinctions between therapies.

Recent Developments in Treatments for Metastatic Castration-resistant Prostate Cancer—A Mechanistic Perspective

2012 ◽  
Vol 08 (02) ◽  
pp. 89
Author(s):  
Guru Sonpavde ◽  
E David Crawford ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Microtubule Inhibitor ◽  
Phase Iii Clinical Trials ◽  
Castration Resistant ◽  
Radium 223

Over the past decade, the treatment landscape in metastatic castration-resistant prostate cancer (CRPC) has markedly changed, with the introduction of three new chemotherapeutic agents. The mechanism of CRPC is not fully understood, but it may result from multiple pathways, including a loss or androgen receptor (AR) specificity and increased downstream signalling activity that provide multiple targets for therapeutic agents. For some years, docetaxel was the mainstay of treatment in CRPC, but recently, cabazitaxel (a microtubule inhibitor), sipuleucel-T (a cancer vaccine), and abiraterone acetate (a CYP17 inhibitor) were approved for CRPC treatment. In Phase III clinical trials, these agents have shown significant improvements in survival—over mitoxantrone (for cabazitaxel) and over placebo (for sipuleucel-T and abiraterone acetate)—and were well tolerated. There are also two treatments in late-stage development, MDV3100 (an oral AR antagonist) and radium-223 (an isotope that creates breaks in double-stranded DNA). These have also shown improvements in survival in Phase III trials; their regulatory approval is expected soon. The modes of actions of the existing and new drugs in CRPC are varied, but some are complementary and investigations of different combinations of these medications are much needed; they may enhance efficacy, further extend survival, and improve outcomes in this formerly untreatable disease.

Management of Castration-Resistant Prostate Cancer: First-Line Therapy

2019 ◽  
Author(s):  
Simon Y.F. Fu ◽  
Kim N. Chi
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Chemotherapeutic Agents ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Radium 223 ◽  
Incurable Condition ◽  
Line Setting

The development of castration-resistant prostate cancer (CRPC) heralds significant morbidity and an incurable condition. Since 2004, there are now six proven life-prolonging therapies available, including androgen receptor pathway inhibitor (ARPI) , chemotherapeutic agents, radiopharmaceutical, and immunotherapy for the first-line management of metastatic CRPC. Recent advances have seen enzalutamide and apalutamide approved by US FDA for the treatment of nonmetastatic CRPC, with darolutamide the latest ARPI demonstrating efficacy in nonmetastatic CRPC. ARPI is the treatment of choice in the first-line setting for most CRPC patients, and this approach has been endorsed by clinical guidelines and expert consensus, although treatment must be individualized. Advances in the molecular profiling of CRPC promise to select suitable patients for trials involving targeted therapy and identify biomarkers to guide treatment selection. This review contains 2 figures, 1 table, and 54 references. Keywords: abiraterone acetate, apalutamide, cabazitaxel, castration-resistant prostate cancer, docetaxel, enzalutamide, first-line treatment, radium-223, sipuleucel-T

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