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The Food and Drug Administration has approved a label update for Zytiga (abiraterone acetate) plus prednisone for patients with metastatic castration-resistant prostate cancer who have not received chemotherapy.

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The new label includes the final analysis data from the Phase III randomized, double-blind, placebo-controlled COU-AA-302 study to evaluate the drug's efficacy. The updated data from that study were presented at the European Society for Medical Oncology Congress last year, and were recently published in Lancet Oncology (OT 3/25/15 issue).


"This analysis adds to the robust body of clinical data supporting Zytiga as an important treatment option for men with metastatic castration-resistant prostate cancer," the study's lead investigator, Charles Ryan, MD, Professor of Clinical Medicine and Urology at the University of California, San Francisco, said in a news release


The updated data showed that Zytiga plus prednisone significantly prolonged median overall survival (34.7 months), compared with placebo plus prednisone in patients (30.3 months), after a follow up of 49.2-months. Additionally, there were no notable changes in the safety profile of Zytiga reported in the final analysis, since the previously reported interim analyses.


Zytiga, marketed by Janssen, works by blocking CYP17-mediated androgen production-which fuels prostate cancer growth-at three sources: in the testes, adrenals, and the prostate tumor tissue. Initial approval of the drug for the treatment of patients with metastatic castration-resistant prostate cancer was based on data from a second interim analysis of the COU-AA-302 study, which included 1,088 men with metastatic castration-resistant prostate cancer who had not received prior chemotherapy (OT 5/25/11 issue).


The drug is not indicated for use in women. The most common adverse reactions (occurring in more than 10% of patients) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and contusion.


The most common laboratory abnormalities (more than 20% of patients) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT, and hypokalemia.


In other recent actions, the FDA granted Orphan Drug designation to two drugs: CRS-207 for the patients with malignant pleural mesothelioma who have not had prior therapy and who are not eligible for surgical resection; and IMO-8400, an antagonist of the endosomal Toll-like receptors (TLRs) 7, 8 and 9, to treat patients with diffuse large B-cell lymphoma (DLBCL).


CRS-207, made by Aduro Biotech, expresses the tumor-associated antigen mesothelin, which is over-expressed in mesothelioma and pancreatic, non-small-cell lung, ovarian, and gastric cancers.


The drug, for use in combination with GVAX Pancreas immunotherapy, previously received Breakthrough Therapy status for the treatment of patients with pancreatic cancer (OT 8/25/14 issue).


CRS-207 is currently being evaluated for use in combination with standard-of-care chemotherapy in a Phase Ib clinical trial of 16 patients. Interim results from the study found that 12 of the patients had a partial response to the treatment and three had stable disease. Based on these initial findings, an expansion cohort of 40 additional patients was opened and is still enrolling.


Regarding IMO-8400, a news release from the manufacturer, Idera Pharmaceuticals, notes that the company is conducting a clinical trial of the agent in patients with relapsed or refractory DLBCL harboring MYD88 L265P oncogenic mutation.


Preclinical trials have shown that in B-cell lymphomas characterized by the MYD88 L265P oncogenic mutation, including DLBCL, TLR signaling is over-activated, allowing tumor cell survival and proliferation.


The new trial's objectives are to evaluate the safety, tolerability, and clinical activity of the three dose-escalation groups of IMO-8400 administered subcutaneously.


"We continue to advance our efforts in DLBCL, as well as our ongoing clinical trial in Waldenstrom's macroglobulinemia, which we expect to complete and have full data available in the fourth quarter of this year," said Idera's Interim Chief Medical Officer, James J. O'Leary, MD.