“Olaparib (Lynparza) has received an FDA breakthrough therapy designation as a treatment for patients with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer (mCRPC) in those who have received a prior taxane-based chemotherapy and at least either hormonal agent enzalutamide (Xtandi) or abiraterone acetate (Zytiga).
“The designation, which will accelerate the development and review of the first-in-class oral PARP inhibitor, is based on data from the phase II TOPARP-A trial that demonstrated that olaparib monotherapy had an overall response rate (ORR) of nearly 90% in a biomarker-defined subgroup of patients who had DNA-repair defects.“
“Clinical trials are now assessing how to best use radium-223 (Xofigo) in combination with androgen inhibitors, following the rapid approval of several agents for men with castration-resistant prostate cancer (CRPC).
“In the first of these studies, a phase III being conducted by the European Organisation for Research and Treatment of Cancer (EORTC), single-agent enzalutamide (Xtandi) is being compared with radium-223 plus enzalutamide for men with asymptomatic or mildly symptomatic bone metastatic CRPC (NCT02194842). Additionally, this same approach is being examined in a phase II study conducted by the All Ireland Cooperative Oncology Research Group (NCT02225704).”
“From its approval in May 2013 to recently being considered as a combination treatment with other drugs, radium-223 dichloride (Xofigo) shows great potential in positively impacting treatment for metastatic castration-resistant prostate cancer (mCRPC), according to Michael Morris, MD, medical oncologist, Memorial Sloan Kettering Cancer Center.
‘This drug has been shown to prolong survival and improve quality of life in men with mCRPC. It improves overall survival; therefore, it helps patients live longer. It also delays complications related to bone metastases, known as SSE. These include bone fracture, bone pain, spinal cord compression, and others. Nevertheless, the drug is not only helping patients live longer, but it is helping them live better, as well,’ said Morris in an interview with Targeted Oncology.”
Most of the recent developments in prostate cancer treatment have addressed the timing and duration of androgen deprivation, who should receive radiation treatments, and the timing of the few available chemotherapy options. But this month’s big news is a welcome change: metastatic castration-resistant prostate cancers (mCRPCs) that harbor mutations in BRCA2 or one of a few other genes have a remarkable response to olaparib (Lynparza), a drug that inhibits the enzyme PARP1. Continue reading…
“The explosion of new drugs for the treatment of castration-resistant prostate cancer (CRPC) is a welcome advance, but raises questions about how best to sequence these drugs with standard docetaxel chemotherapy. A subanalysis of the ALSYMPCA trial suggests that chemotherapy can be safely administered after treatment with radium-223—one of the newer agents approved in this setting—in patients with metastatic CRPC and bone metastasis.
“The study, presented at the 18th ESMO-40th ECCO 2015 European Cancer Congress, was a post-hoc analysis of patients enrolled in ALSYMPCA who received chemotherapy post treatment with radium-223 and post treatment with placebo. Follow-up was 3 years.
“ ‘This study has some limitations, including the fact that it represents a subset of patients based on post-randomization factors, including study drug treatment with radium-223 or placebo, and randomization of the original study does not ensure comparability of the treatment arms,’ said lead author Oliver Sartor, MD, Tulane Cancer Center, New Orleans, LA.”
“Patients who received hormonal regimens for the treatment of castration-resistant prostate cancer experienced a significant increase in incidence of and relative risk for cardiovascular toxicity, according to results of a meta-analysis.
“Roberto Iacovelli, MD, medical oncologist in the division of urogenital and head and neck tumors at European Institute of Oncology in Milan, and colleagues sought to define the incidence and RR of cardiovascular events in a population of patients treated with new hormonal therapies for metastatic castration-resistant prostate cancer.
“Incidence of all-grade toxicities (grades 1-4) and high-grade toxicities (grade 3-4) served as the primary outcome of the study.
“Iacovelli and colleagues identified six prospective phase 2 or phase 3 studies that included a total of 7,830 patients. Within each study, researchers considered treatment with a novel hormonal agent plus prednisone in the experimental arm (n = 4,520) and placebo plus prednisone (n = 3,310) as the control.”
“Fred Saad, MD, FRCS, professor, Department of Surgery, University of Montreal, discusses the use of radium-223 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
“The approved indication for radium-223 is in patients with metastatic disease to the bone, but no visceral disease. Patients should also demonstrate symptoms, though they do not need to be in significant pain, Saad explains. If patients wait too long to seek treatment, they are less likely to receive all six cycles of treatment and the added survival benefit.
“Researchers have not witnessed negative effects associated with administering radium-223 into earlier lines of therapy, Saad says. Compared with other treatments, few adverse events occurred with radium-223 in the international early access program. The treatment is also said to be well-tolerated regardless of disease stage.”
“For more than a decade, oncologists using cytotoxic chemotherapy to treat patients with advanced metastatic castration-resistant prostate cancer (mCRPC) have relied on the sequential use of single agent taxanes such as docetaxel and cabazitaxel. For example, docetaxel is commonly used as the ‘first-line’ therapy, while cabazitaxel is used as the ‘second-line’ therapy. A role for combination therapy using two or more chemotherapy agents at the same time has not been well studied. This week, however, results of a clinical trial presented at the American Society of Clinical Oncology meeting by researchers at The University of Texas MD Anderson Cancer Center may change the perspective on a role for combination chemotherapy in advanced disease.
“The study compared the effectiveness of cabazitaxel alone versus cabazitaxel combined with carboplatin – a type of platinum chemotherapy—in patients with metastatic castrate-resistant prostate cancer (mCRPC). To date, 160 men have been randomized to treatment with either the single or dual chemotherapy drug regimen. Each patient received up to 10 cycles of chemotherapy.
“Innocrin Pharmaceuticals, Inc., a clinical-stage pharmaceutical company developing small-molecule CYP17 lyase-selective inhibitors for the treatment of hormonally-dependent breast and prostate cancers resistant to standard hormonal therapy, today announced the initiation of a new Phase 2 study: Once-daily Oral VT-464 in Patients With CRPC Progressing on Enzalutamide or Abiraterone (clinicaltrials.gov/ct2/show/NCT02445976). The trial is led by Howard Scher, MD, Chief of Genitourinary Oncology Service at Memorial Sloan Kettering, who is the recipient of a prestigious $1 million Challenge Award from the Prostate Cancer Foundation (PCF). Dr. Scher is a recognized leader of a ‘personalized medicine’ approach for CRPC, the goal being to deliver the right drug to patients at the right time.”