Janssen's Zytiga Boosts Survival in Early-Stage Prostate Cancer

“Janssen has announced data from a post-hoc analysis of a Phase III trial showing that Zytiga plus prednisone boosted overall survival (OS) by 11.8 months compared with placebo plus prednisone, in men with early and less aggressive metastatic castration-resistant prostate cancer (mCRPC) who had not received chemotherapy.

“Data presented today at the European Association of Urology (EAU) 2016 Congress in Munich, Germany, demonstrated that in the COU-AA-302 trial, Zytiga (abiraterone acetate) increased OS to 53.6 months versus the 41.8 months achieved by patients treated with prednisone alone. This benefit was shown to be 4.4 greater than that previously reported for the combo in the final analysis of the COU-AA-302 trial in 2014.

“The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in group 1 were in an earlier, less advanced and less symptomatic stage of the disease, while those in group 2 were in a later, more advanced and more symptomatic stage of the disease.”


Abituzumab Improves Bone Lesion Progression, not PFS in CRPC

“Abituzumab did not extend progression-free survival (PFS) compared with placebo in a phase II study of patients with metastatic castration-resistant prostate cancer. The agent did, however, offer a lower incidence of bone lesion progression, and researchers say it still warrants further investigation.

“Previous research has suggested that integrins play a role in the progression of metastatic prostate cancer and associated bone lesions, wrote researchers led by Maha Hussain, MB, ChB, of the University of Michigan in Ann Arbor. Abituzumab is a pan-αv integrin inhibitor; a phase I trial previously showed that the agent has activity in patients with castration-resistant prostate cancer and bone metastases.

“The new phase II trial randomized 180 patients between three arms: a 750-mg abituzumab group, a 1,500-mg abituzumab group, or placebo. All groups also received standard of care. The results were published in Clinical Cancer Research.”


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.


Radium-223 Benefits Survival, Not Just for Palliative Care

“Despite what many believe, not all radiopharmaceuticals are just for pain palliation, says Phillip J. Koo, MD, a radiologist of Memorial Hospital and University of Colorado Hospital.

“The ALSYMPCA trial, which was the basis for the 2013 FDA approval of radium-223 dichloride (Xofigo) showed a median overall survival (OS) of 14 months with radium-223 versus 11.2 months with placebo (HR, 0.70; P = .00185) in patients with metastatic castration-resistant prostate cancer (mCRPC).

“Despite the fact that it has been 3 years since the pivotal ALSYMPCA trial and the coinciding FDA approval, many oncologists still need to be educated regarding radium-223’s benefits, says Koo.”


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.”


Hormonal Drugs for Prostate Cancer Increase Risk, Incidence of Cardiovascular Events

“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.”