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PER Pulse™ Recap
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PER Pulse™ Recap
Clinical Considerations for Patients with Hormone-Sensitive, Metastatic Prostate Cancer
The treatment paradigm for patients with metastatic prostate cancer continues to evolve, with several recent studies providing new information regarding options for patients with hormone-sensitive prostate cancer, as well as those who have castration-resistant prostate cancer (CRPC). Androgen-deprivation therapy (ADT) has been a historical cornerstone of treatment for patients with hormone-sensitive, metastatic prostate cancer, a group that accounts for approximately 3% of new prostate cancer diagnoses.1-3 One key STAMPEDE phase III study compared long-term hormone therapy (standard of care [SOC]) versus SOC plus zoledronic acid versus SOC plus docetaxel versus SOC, zoledronic acid, and docetaxel.5 Median survival with the combination of docetaxel and ADT was 81 months compared with 71 months with ADT alone, leading to the incorporation of docetaxel into the SOC for appropriate patients who are hormone treatment‒naïve.4,5
The recent phase III, randomized, controlled CHAARTED trial3 assessed the addition of docetaxel to standard ADT for the treatment of patients with metastatic ADT-naïve disease. This study showed that the combination of ADT plus docetaxel was associated with improved outcomes compared with ADT alone (median overall survival OS [OS], median time to clinical progression, and development of metastatic castration-resistant prostate cancer [mCRPC]).3 The phase III LATITUDE trial1 has also recently assessed the efficacy of abiraterone acetate plus prednisone with ADT versus ADT plus placebo in patients with newly diagnosed metastatic prostate cancer, showing benefits with respect to OS and radiographic progression-free survival (rPFS).1 Furthermore, significant improvements were seen in the group treated with abiraterone with respect to multiple other outcomes, including time until pain progression, prostate-specific antigen (PSA) progression, symptomatic skeletal-related events (SREs), initiation of chemotherapy, and subsequent prostate cancer therapy1
Dr Beer provides his perspectives on recent advancements in the treatment of patients with metastatic castration-sensitive prostate cancer. With respect to the role of chemotherapy in metastatic castration-sensitive prostate cancer, large randomized trials have shown an improvement in OS with the addition of 6 cycles of docetaxel to ADT. When available, subset analyses (including those that are prospectively stratified) have shown evidence of benefit in patients with more-extensive disease, particularly those with de novo metastatic disease. The benefit of chemotherapy in nonmetastatic disease remains to be established, as does the benefit of chemotherapy in patients with low-volume metastatic disease.
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PER Pulse™ Recap
Management Approaches for Patients with Early Metastatic CRPC
When selecting an agent for first-line therapy for a patient with metastatic castration-resistant prostate cancer , several factors need to be considered. Disease-related factors include symptoms that the patient is experiencing, performance status , sites of metastases, duration of prior androgen-deprivation therapy , as well as other prior treatment regimens. Patient-related factors include age, comorbidities, toxicity concerns, cost concerns, and patient preference for options, such as route of medication administration. There are several treatment options which are reviewed for patients with castration-resistant prostate cancer , including sipuleucel-T, abiraterone, enzalutamide, radium-223, and chemotherapy. Several recent studies such as ALSYMPCA, PREVAIL, and IMPACT have helped to shed light on safety and efficacy of these therapies, as well as other factors which may influence treatment selection.1-12 Dr Sonpavde provides his perspectives on different treatment options, sequencing considerations, and treatment-related toxicity management for these patients.
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PER Pulse™ Recap
Optimizing Treatment for Patients with Metastatic CRPC
When considering treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), it is important to consider not only site of metastases, but also symptoms that the patient is experiencing when selecting treatment options. Control of pain is important for all patients, particularly those with bony metastases. Palliative radiotherapy (RT) may be appropriate for bony metastases associated with prostate cancer1,2; single lesions may be managed with external-beam RT (EBRT). According to therapeutic guidelines from the American College of Radiology, most patients should be treated with a single course of 8 Gy for metastases that are not vertebral.3 However, patients with diffuse disease are candidates for systemic therapy.
Several treatments have been approved to control pain or have specific indications for patients who are symptomatic, including radiopharmaceuticals, the combination of mitoxantrone plus prednisone, samarium-153, and radium-223 (for patients whose symptoms arise from bone metastases). Beta-emitters, such as samarium-153 and strontium-89, are commonly used for painful bony metastases, but these do not improve survival.1 Radium-223 has been shown to prolong overall survival (OS), as well as time to first symptomatic skeletal-related event (SRE). In the phase III ALSYMPCA study,2 the median OS and median time to first symptomatic SRE were significantly greater for patients who received radium 223 compared to those treated with placebo. Abiraterone and enzalutamide have also been studied in the treatment of patients with CRPC who have symptomatic bony metastases,3,4 and Dr Scher provides his perspectives on data that have helped to govern his treatment selections for these patients. He also discusses treatment monitoring and other factors that may help to optimize patient outcomes.
Approximately 25% of patients with mCRPC have visceral metastases. Many treatment options have been studied in this patient population, and Dr Higano discusses the evidence from key studies such as PREVAIL and AFFIRM.5,6 Liver and lung metastases should be considered separately. In both the PREVAIL and AFFIRM studies, patients with liver metastases had a much worse prognosis, whereas the OS in patients with lung metastases was similar to those who had only bone metastases.5,6 The presence of visceral metastases is associated with poor survival, but does not necessarily mean that the patient will not be likely to respond to therapy.7 Furthermore, the prevalence of visceral disease in these patients increases over time, and often there is a discordance between prostate-specific antigen and radiological progression of visceral disease.7 When visceral metastases are identified, biopsy may help to determine histological and molecular characterization of tumors and guide treatment selection, as there is sometimes discordance between archival and fresh tissue.7 Tumor heterogeneity further contributes to the complexity of analysis and treatment decisions.