Optimizing Treatment With Radium-223 for Prostate Cancer

Excerpt:

“As oncologists await future treatment advances in metastatic castration-resistant prostate cancer (mCRPC), the key is to unleash the full potential of available therapies, Robert Dreicer, MD, asserted during the 2016 CFS Chemotherapy Foundation Symposium.

“One agent that oncologist are focused on optimizing, Dreicer said, is radium-223 (Xofigo). Optimal use of this treatment remains mostly unknown, with current efforts focusing on exploring the agent’s potential in combination regimens.

“For instance, a phase III trial is randomizing patients with bone predominant mCRPC to radium-223 plus abiraterone acetate (Zytiga) or abiraterone alone (NCT02043678). Additionally, a randomized phase IIa study is evaluating the efficacy and safety of radium-223 in combination with abiraterone or enzalutamide (Xtandi) in patients with mCRPC to investigate bone-scan response, radiological progression-free survival, overall survival, and skeletal events (NCT02034552).”

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New Therapeutic Agent Proves More Effective Treatment for Advanced Prostate Cancer

Excerpt:

“A German multicenter study, initiated by the German Society of Nuclear Medicine, demonstrates that lutetium-177 (Lu-177)-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). The study is published in the January 2017 issue of the Journal of Nuclear Medicine and is the featured article.

“Prostate-specific membrane antigen (PSMA) is overexpressed in and even more so with castration-resistant disease. This makes development of new tracers for PSMA-targeted radionuclide therapies a promising treatment approach. Prostate cancer deaths are usually the result of mCRPC, and the median survival for men with mCRPC has been less than two years.”

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How Highs and Lows in Testosterone Levels ‘Shock’ Prostate Cancer Cells to Death

Excerpt:

“Munich, Germany: A strategy of alternately flooding and starving the body of testosterone is producing good results in patients who have metastatic prostate cancer that is resistant to treatment by chemical or surgical castration, according to new findings.
“In a presentation at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany, today (Thursday), researchers reported that results from 47 men who have completed at least three cycles of bipolar androgen therapy (BAT) showed that the strategy was safe and effective. Prostate specific antigen (PSA) levels fell in the majority of the men, tumours shrank in some men, in several the disease did not progress and this included some whose disease continued to be stable for more than a year. One man appears to have been ‘cured’, in that his PSA levels dropped to zero after three months and have remained so for 22 cycles of treatment, with no trace of the disease remaining. The researchers are planning to treat a group of 60 men in total.”

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Cabazitaxel/Abiraterone Combination Promising in mCRPC

Excerpt:

“The combination of cabazitaxel and abiraterone was well tolerated and showed antitumor activity in previously treated patients with metastatic castration-resistant prostate cancer (mCRPC), according to a new phase I/II study.

” ‘Therapeutic options for men with mCRPC have evolved considerably with the approval of five therapies associated with improved overall survival,’ wrote study authors led by Christophe Massard, MD, PhD, of Gustave Roussy Cancer Campus in Villejuif, France. Still, ‘there is a need to provide robust evidence on how these agents should be used, in sequence or in combination, to achieve optimal medical management.’ ”

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Adding Bone Drugs to Radium-223 May Enhance Benefit in mCRPC

Excerpt:

“Men with bone-metastatic castration-resistant prostate cancer (mCRPC) appeared to derive additional benefits from treatment with radium-223 with concomitant bone-targeted therapies, according to data from an extended-access program.

“After a median follow-up of 7.5 months from initial injection of radium-223, patients on concomitant denosumab had yet to reach a median overall survival (OS), whereas patients treated with radium-223 alone had a median survival of 13.4 months.”

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Enzalutamide Shows Efficacy in Prostate Cancer With Visceral Mets

Excerpt:

“Patients with metastatic castration-resistant prostate cancer (mCRPC) and visceral metastases (liver and lung) fare better with the androgen receptor inhibitor enzalutamide than placebo, according to a new analysis from the phase III AFFIRM trial. There were differences in response based on which of those two sites had metastases, suggesting they should be considered differently for treatment.

” ‘Visceral metastases are identified in approximately 22% to 30% of patients with mCRPC and are associated with unfavorable outcomes,’ wrote study authors led by Yohann Loriot, MD, PhD, of Université Paris-Saclay in Villejuif, France.”

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Video: An Overview of the ALSYMPCA Study in Metastatic Prostate Cancer

Excerpt:

“Luke Nordquist, MD, FACP, a urologic medical oncologist and CEO of the Urology Cancer Center and GU Research Network, gives an overview of the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) study, and he discusses ongoing trials examining the use of radium-223 dichloride (Xofigo) in metastatic castration-resistant prostate cancer (mCRPC).”

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Custirsen Combo Falls Short in Phase III mCRPC Trial

Excerpt:

“Adding custirsen to cabazitaxel (Jevtana) and prednisone in the second-line setting failed to improve overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) in the phase III AFFINITY trial, according to OncoGenex, the company developing the drug.

“The open-label AFFINITY trial included 634 men with mCRPC who progressed on docetaxel. Patients were randomized to cabazitaxel plus prednisone with or without weekly custirsen. Treatment was administered until progression, unacceptable toxicity, or the completion of 10 cycles. The study was conducted at 95 locations in North America, Europe, Russia, and Australia.”

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Pivotal ARMOR 3-SV Prostate Cancer Trial Discontinued After PFS Rates Miss the Mark

Excerpt:

“The pivotal phase III prostate cancer trial ARMOR 3-SV will be discontinued based on recommendations made by the trial’s independent data monitoring committee (DMC), according to the manufacturer Tokai Pharmaceuticals. The DMC concluded that ARMOR 3-SV would unlikely meet its primary endpoint of demonstrating improved radiographic progression-free survival (PFS) based on its review of all safety and efficacy data. Top-line data from the trial is not expected until next year.

“It’s a big setback for the company, which was seeking the right niche for the agent in a crowded prostate cancer treatment market. ARMOR 3-SV compared galeterone with enzalutamide (Xtandi) in patients with treatment-naïve metastatic castration-resistant prostate cancer (mCRPC), particularly in patients whose prostate tumors expressed AR-V7. These truncated ARs are missing the C-terminal end of the AR that contains the ligand-binding domain, which is known as C-terminal loss. AR-V7 is the most common form of C-terminal loss of androgen receptors (ARs), a key target in resistance. This form of AR-V7 is also thought to make patients unlikely to respond to either enzalutamide or abiraterone acetate (Zytiga).”

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