Expert Says Xofigo Is "Game Changer" for Bone Metastatic CRPC


“Radium-223 dichloride (Xofigo) opened an entirely new chapter in the treatment landscape of castration-resistant prostate cancer with bone metastases (mCRPC), says E. David Crawford, MD, professor of Radiation Oncology, Department of Surgery, at the University of Colorado Denver.

“ ‘Radium-223 is sort of a surprise drug, at least to me,’ says Crawford. “We have had radioisotopes around for a long period of time, including phosphorus-32, samarium-153 (Quadramet), strontium-89 (Metastron), and others. But, they all had a lot of baggage with them, in terms of side effects.

” ‘Now, we have a new one—radium-223—which is not associated with the side effects that we were seeing with the other ones, but it is associated with an improvement in survival rate. It’s a game changer.’ ”

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Radium-223 Improves QoL Over Placebo in CRPC

“Analyses from the phase III ALSYMPCA trial showed that treatment with the alpha-emitting radiopharmaceutical radium-223 resulted in quality-of-life (QoL) improvements over placebo in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases.

“ ‘Patients with CRPC and bone metastases often present with symptoms such as pain fatigue, anorexia, and, rarely, spinal cord compression, contributing to rapid and significant deterioration in health-related QoL and mortality,’ wrote study authors led by Sten Nilsson, MD, PhD, of Karolinska University Hospital in Stockholm.

“The ALSYMPCA trial found that radium-223 prolonged overall survival (OS) as well as time to first symptomatic skeletal event by significant periods. The trial included prospective QoL measurements using the EuroQoL EQ-5D and the Functional Assessment of Cancer Therapy–Prostate (FACT-P). The results from these tests were published online ahead of print in Annals of Oncology.”

Precision Medicine on the Horizon for Prostate Cancer

“While still in its early stages, integrative genomic testing could be the future for personalizing therapy for patients with castration-resistant prostate cancer (CRPC), according to Tomasz M. Beer, MD, FACP.

“In an interview with Targeted Oncology, Beer, deputy director, Knight Cancer Institute, Oregon Health and Science University, explained that understanding the genetic makeup of CRPC could lead to new treatments, both single-agents and combinations. One of the most recent examples was the discovery of BRCA genetic mutations within CRPC, he said. While BRCA mutations are mostly associated with breast and ovarian cancers, this discovery could provide a new avenue for treating men with CRPC.

“In the interview, Beer discussed the current state of genetic testing for prostate cancer and changes on the horizon that are currently being explored in clinical trials.”

Enzalutamide Superior to Bicalutamide for Castration-Resistant Prostate Cancer

“The oral androgen receptor inhibitor enzalutamide significantly reduced the risk for prostate cancer progression or death compared with bicalutamide in patients with castration-resistant prostate cancer, according to findings from the STRIVE trial.

“Enzalutamide (Xtandi, Astellas) has been found to improve survival in men with castration-resistant prostate cancer prior to and following chemotherapy. It binds the androgen receptor in the same way as bicalutamide does, but with greater affinity, according to researchers.

“Since bicalutamide is the standard treatment for this population of patients, researchers conducted this phase 2 trial to compare the two treatments.”

FDA Grants Olaparib Breakthrough Designation in mCRPC

“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.

Multiple Trials Explore Radium-223 Combinations for mCRPC

“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).”

The Potential of Radium-223 as a Treatment in mCRPC

“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.”

Finally: An Active Prostate Cancer Drug That Doesn’t Target Androgen

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…

Chemotherapy After Radium-223 Safe in Metastatic Castration-Resistant Prostate Cancer

“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.”