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Novel Concepts Include New Agents, Combinations

Anita T. Shaffer @Shaffer1
Published: Tuesday, Jun 19, 2012
Dr. Oliver Sartor

Oliver Sartor, MD

Oncology specialists who treat patients with metastatic castration-resistant prostate cancer (mCRPC) can look forward to choosing from an expanding array of therapeutic tools, including regimens that couple immunotherapy with novel agents and radiation, according to Oliver Sartor, MD.

During his presentation at IPCC, Sartor noted that patients with prostate cancer likely will require multiple drugs to achieve cure rates, just as “it takes four drugs to cure Hodgkin disease, one of our most curable malignancies.”

“I think we’re all looking forward to the day when we can start to combine these agents,” said Sartor, who is medical director and a professor in the Department of Medicine, Section of Hematology & Medical Oncology at the Tulane Cancer Center in New Orleans, Louisiana.

As it stands now, Sartor said there have been six phase III trials either completed in recent years or with interim results in which a survival advantage has been demonstrated in mCRPC (Table).

Novel therapeutics also are in development. Sartor reviewed agents involving these four concepts: immunotherapy, with ipilimumab (Yervoy; Bristol- Myers Squibb) and PROSTVAC-VF-TRICOM (Bavarian Nordic); the targeted alpha-emitter, radium-223 (Alpharadin; Bayer HealthCare); an inhibitor of c-MET and vascular endothelial growth factor receptor 2 (VEGFR-2), cabozantinib (formerly XL184; Exelixis); and the RANK ligand inhibitor and bone-strengthening agent denosumab (Xgeva; Amgen).

Table. Phase III Trials in Metastatic CRPC With a Survival Advantage

Trial Design HR Survivala (months) Differences
TAX 327
N = 1006
Docetaxel/prednisone vs mitoxantrone/prednisone 0.76 18.9 vs 16.5 2.4 months
IMPACT
N = 512
Sipuleucel-T vs control cells 0.78 25.8 vs 21.7 4.1 months
TROPIC
N = 755
Cabazitaxel/prednisone vs mitoxantrone/prednisone 0.70 15.1 vs 12.7 2.4 months
COU-301
N = 1195
Abiraterone/prednisone vs placebo/prednisone 0.65 14.8 vs 10.9 3.9 months
ALSYMPCA
N = 922
Radium-223 + best standard of care (BSC) vs placebo/BSC 0.70 14.9 vs 11.3b 3.6 months
AFFIRM
N = 1199
MDV3100 vs placebo 0.63 18.4 vs 13.6 4.8 months

aSurvival outcomes are not directly comparable because the trials varied on whether docetaxel was administered. Participants in the TAX 327, TROPIC, COU-301, and AFFIRM trials received docetaxel, while most participants in the IMPACT trial did not. Participants in ALSYMPCA either were treated with docetaxel, not a candidate for docetaxel, or received patient's/physician's choice.
b Represents updated data not yet presented.

Sartor O. Immunomodulatory and bone targeted therapeutics in metastatic castrate-resistant prostate cancer. Presented at: 5th Annual Interdisciplinary Prostate Cancer Congress (IPCC); March 31, 2012; New York, NY.

Immunotherapies

In the area of immunomodulatory therapies in prostate cancer, Sartor said he is “particularly excited” about the prospects for ipilimumab and the PROSTVAC-VF-TRICOM vaccine.


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Personalized Sequencing in Castration-Resistant Prostate Cancer: Bridging the Latest Evidence to the Bedside in Clinical ManagementAug 25, 20181.5
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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