Skip to main content

New Treatment Options for Castration-Resistant Prostate Cancer

August 2011 Vol 4, No 4, Special Issue - Prostate Cancer

With the recent US Food and Drug Administration (FDA) approval of 4 new agents for patients with castration-resistant prostate cancer (CRPC), more options to extend life or prevent cancer treatment–associated skeletal-related events (SREs) are now available.

Kim Chi, MDIn addition to the new 4 drugs— sipuleucel-T (Provenge), denosumab (Prolia), cabazitaxel (Jevtana), and abiraterone (Zytiga)—a number of other agents are currently in latestage clinical trials and promise to change how prostate cancer is treated, said Kim Chi, MD Associate Professor of Medicine, University of British Columbia, Vancouver.

New therapies are evolving “across a diversity of targets, including androgen signaling, chaperone proteins, DNA repair, apoptosis, and a whole host of cell signaling from cell-surface receptors to intracellular signaling,” said Dr Chi.

Sipuleucel-T An immune response to cancer occurs in the same way as any adaptive immune response, said Charles Drake, MD, PhD, Assistant Professor of Oncology, Immunology, and Urology, Johns Hopkins University, Baltimore. Sipuleucel-T is thought to focus on activated dendritic cells, which present their target antigens to CD4 and CD8 T-cells, “upregulating the cytotoxic machinery.” Sipuleucel-T is an “active” cellular immunotherapy, using patients’ own white blood cells as part of its mechanism of action.

In the IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial that led to the drug’s approval, asymptomatic patients who received sipuleucel-T had a median overall survival (OS) benefit of 4.1 months over placebo. The drug is indicated for men with minimally symptomatic meta - static CRPC.

Investigational Agents

A viral vaccine approach (PROSTVAC- VF) is currently in development for CRPC, Dr Drake added. The fully human monoclonal antibody ipilimumab (Yervoy), recently approved by the FDA for the treatment of metastatic melanoma, is also being evaluated for this patient population.

Denosumab

Many factors militate against healthy bone in men with prostate cancer, said Thomas Flaig, MD, Assistant Professor, University of Colorado, Denver. Besides androgen deprivation and the use of glucocorticoids, tumors themselves contribute to osteoporosis.

Denosumab is a fully human monoclonal antibody and osteoclast inhibitor. It inhibits the RANK-ligand, the activator of osteoclastic activity that is upregulated by tumor growth. There is less concern for renal toxicity with denosumab than with zoledronic acid (Zometa, Reclast). “For those patients with renal insufficiency, I think this will be a very good option,” said Dr Flaig.

Osteonecrosis of the jaw and hypocalcemia, however, are still a risk. In a study comparing denosu - mab with zoledronic acid, denosu - mab extended the time to a first SRE by a median of 3.6 months compared with zoledronic acid.

Denosumab is approved for the prevention of SREs in patients with bone metastases from solid tumors.

Cabazitaxel

Cabazitaxel is a microtubule in - hibitor and traditional cytotoxic chemotherapy agent, Dr Drake said. In the phase 3 TROPIC trial, which addressed metastatic CRPC that progressed in patients who initially received docetaxel chemotherapy, the median OS in patients who received cabazitaxel was 15.1 months compared with 12.7 months for those who received mitoxantrone.

Cabazitaxel was associated with more bone marrow suppression than mitoxantrone, and with higher rates of neutropenia and febrile neutropenia. Febrile neutropenia occurred in 8% of patients receiving cabazitaxel versus 1% with mitoxantrone. In addition, there is a risk of early infectious disease with cabazitaxel, which led to more deaths than with mitoxantrone (4.9% vs 1.9%).

Cabazitaxel is approved for use with prednisone for the treatment of meta - static CRPC previously treated with docetaxel.

Abiraterone

With chemical or surgical castration, testosterone (or androgen) levels are reduced by 90% to 95%, but not to zero, said Dr Flaig. In addition, tumor tissue produces testosterone.

Abiraterone is a CYP17 inhibitor that blocks all testosterone production. In patients with metastatic CRPC who had received 1 or 2 courses of chemotherapy, including docetaxel, abiraterone significantly improved OS compared with placebo (14.8 months vs 10.9 months, respectively).

Mineralocorticoid excess, fluid re - tention, hypokalemia, and cardiac disorders are some adverse effects of the drug.

Abiraterone is approved for use with prednisone for metastatic CRPC after initial therapy with docetaxel. “So here is a very well-tolerated oral drug that has given a survival advantage—really, a hormonal drug—in the postchemo - therapy setting,” Dr Flaig added.

New Standard of Care

“What a difference a year makes,” said Dr Flaig when discussing the new standards of care. “Sipuleucel-T now has a strong indication for a survival benefit for patients with metastatic, minimally symptomatic CRPC. Once patients have progressed while using docetaxel, there are some great options—abiraterone, with a 4-month survival advantage, or cabazitaxel…. And denosumab has been shown to be superior to zoledronic acid in preventing the first SRE.”

Related Items
¹⁷⁷Lu-PSMA-617 Prolongs Survival in Patients with Metastatic Castration-Resistant Prostate Cancer
Phoebe Starr
August 2021 Vol 14, Special Issue: Payers' Perspectives in Oncology published on August 9, 2021 in Prostate Cancer, Conference Highlights ASCO
¹⁷⁷Lu-PSMA-617 Superior to Cabazitaxel in Metastatic Prostate Cancer
Phoebe Starr
Web Exclusives published on June 7, 2021 in Prostate Cancer
Cabozantinib plus Atezolizumab Combination Shows Meaningful Activity in Metastatic Prostate Cancer
Phoebe Starr
August 2020 Vol 13, Special Issue: Payers' Perspectives in Oncology published on August 17, 2020 in Prostate Cancer
Oral Relugolix Equals Standard ADT, Slashes Cardiac Events in Patients with Advanced Prostate Cancer
Phoebe Starr
August 2020 Vol 13, Special Issue: Payers' Perspectives in Oncology published on August 17, 2020 in Prostate Cancer
Early Phase 2 Data Promising for Lutetium-177 PSMA-617 in Metastatic Prostate Cancer
Phoebe Starr
August 2020 Vol 13, Special Issue: Payers' Perspectives in Oncology published on August 17, 2020 in Prostate Cancer
Last modified: August 30, 2021