German Agency: Provenge No Better than Watchful Waiting, Standard Hormone Therapy for Some Men with Metastatic Prostate Cancer

The gist: The drug sipuleucel-T (Provenge) may be no better than watchful waiting and standard androgen deprivation therapy for certain prostate cancer patients. That was the conclusion of the German Institute for Quality and Efficiency in Health Care (IQWiG). The IQWiG analyzed data on men with metastatic prostate cancer who had few or no symptoms and did not yet need chemotherapy.

“Sipuleucel-T (trade name Provenge) has been approved since September 2014 for men with metastatic prostate cancer who have few or no symptoms and do not yet require chemotherapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether the drug offers patients an added benefit over one of the appropriate comparator therapies.

“According to the findings, an added benefit is not proven: The data on mortality were not evaluable because differences between the treatment groups might have been caused by the circumstances of the subsequent therapies. At the same time, certain side effects such as fever occur more frequently.

“Treatment with sipuleucel-T aims to stimulate the immune system to kill cancer cells. Immune cells are extracted from the patient’s blood and treated with a protein in a laboratory. These treated cells are then injected back into the patient’s blood where they are supposed to better recognize cancer cells and stimulate the immune system to fight the prostate cancer.

“Sipuleucel-T is an option for patients whose cancer has already formed metastases and can also no longer be influenced by blocking the hormone testosterone (hormone refractory).”


Karyopharm Announces Initiation of Phase 2 Study of Selinexor (KPT-330) in Patients with Hormone Refractory Prostate Cancer (SHIP Study)

“Karyopharm Therapeutics Inc., a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport targets for the treatment of cancer and other major diseases, today announced the initiation of a Phase 2 trial of its novel, oral Selective Inhibitor of Nuclear Export (SINE) compound Selinexor (KPT-330) in patients with metastatic hormone-refractory prostate cancer (HRPC). The study, referred to as the SHIP (Selinexor in Hormone Refractory Indications in Prostate Cancer) study, is led by Drs. Christopher J. Logothetis and John Araujo of the M.D. Anderson Cancer Center at the University of Texas in Houston and is being funded in part by a grant from the Prostate Cancer Foundation.”

Editor’s note: This story describes a new clinical trial to test a prostate cancer treatment in volunteer patients. The new drug is called Selinexor (aka KPT-330), and it may benefit patients who have been diagnosed with metastatic hormone-refractory prostate cancer.


ASCO: Visceral Spread Guts Prostate Ca Survival Odds

“Lung, liver, and other visceral metastases are associated with the poorest survival in advanced hormone-refractory prostate cancer, according to results from a meta-analysis that sets the benchmark for prognosis.

“Lung metastases were associated with 30% higher adjusted odds of death compared with bone metastases (median survival 17 versus 20 months, P<0.002), Susan Halabi, PhD, of Duke University, and colleagues found.

“Liver metastases were even worse, with 40% higher adjusted odds of death compared with lung metastases after adjustment for performance status, prostate specific antigen (PSA), and age (median 12 months, P<0.001), the group reported here at the American Society of Clinical Oncology meeting.”


lncRNA-Dependent Mechanisms of Androgen-Receptor-Regulated Gene Activation Programs

“Although recent studies have indicated roles of long non-coding RNAs (lncRNAs) in physiological aspects of cell-type determination and tissue homeostasis1, their potential involvement in regulated gene transcription programs remains rather poorly understood. The androgen receptor regulates a large repertoire of genes central to the identity and behaviour of prostate cancer cells2, and functions in a ligand-independent fashion in many prostate cancers when they become hormone refractory after initial androgen deprivation therapy3. Here we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 (also known as PCAT8) and PCGEM1, bind successively to the androgen receptor and strongly enhance both ligand-dependent and ligand-independent androgen-receptor-mediated gene activation programs and proliferation in prostate cancer cells.”