The Lynx Group

Updated NCCN Guideline for Prostate Cancer Allows Early Treatment with Docetaxel

April 2015, Vol 6, No 3

Hollywood, FL—The updated National Comprehensive Cancer Network (NCCN) guideline allows for the upfront use of docetaxel (Taxotere) in some men with castration-resistant prostate cancer (CRPC). This and other systemic therapies represent the most significant changes in the updated guideline for the treatment of patients with metastatic CRPC, said Andrew J. Armstrong, MD, ScM, Co­-Leader, Genitourinary Oncology Research Program, Duke Cancer Institute, Durham, NC, at the 2015 NCCN annual conference.

First-line therapy options in the updated guideline include docetaxel plus prednisone, enzalutamide (Xtandi), and abiraterone (Zytiga) plus prednisone.

“The castration-sensitive guideline ­allows for the early use of docetaxel ­­in high-volume men who present with metastatic disease,” said Dr Armstrong. “Now, instead of just giving ADT [androgen-deprivation therapy], we have 6 cycles of docetaxel, and that’s associated with about a 17-month improvement in survival.”

The data to which he is referring come from the CHAARTED trial, and have not been published but were presented at the 2014 American Society of Clinical Oncology annual meeting. In that study, the median overall survival (OS) was 13.6 months longer when docetaxel was added to ADT compared with ADT alone; in men with high-volume metastatic disease, the median OS was 17.0 months longer with the addition of docetaxel.

In addition, the guideline now reflects level I evidence (from the PREVAIL trial) for the use of enzalutamide, said ­Dr Armstrong. In PREVAIL, which was conducted in men with metastatic CRPC before chemotherapy, the median radiographic progression-free survival (PFS) had not yet been reached in enzalutamide recipients compared with 3.9 months in the placebo group.

The rate of radiographic PFS at 12 months was 65% in the enzalutamide group versus 14% among patients receiving placebo, for an 81% risk reduction with enzalutamide. Furthermore, enzalutamide reduced the risk for death by 29%, and in subsets of men with visceral disease, in whom outcomes are generally worse, enzalutamide delayed PFS.

“We also have a little more stratification based on visceral disease” metastases, said Dr Armstrong. “There are some drugs we can’t use in visceral disease. We have multiple lines of therapy now, so there’s a new page that goes over the appropriate options as the disease progresses.”

The recommendations about immunotherapy in the form of sipuleucel-T (Provenge) also find their way into the guideline, courtesy of the IMPACT trial, in which the median OS was extended by 4.1 months with sipuleucel-T relative to placebo, for a 22% reduction in the risk for death.

The newest version of the guideline also addresses the use of abiraterone acetate plus prednisone, and reflects data from the COU-AA-302 phase 3 registration trial. At the third interim analysis, radiographic PFS was doubled in the abiraterone plus prednisone group compared with the group receiving placebo plus prednisone (16.5 vs 8.3 months), representing a 48% reduction in risk with abiraterone. The median OS was also significantly superior with randomization to abiraterone; the median OS was not yet reached in the abiraterone group and was 27.2 months in the placebo group, corresponding to a hazard ratio of 0.57.

Several ongoing phase 3 trials in CRPC have the potential for practice-changing results, said Dr Armstrong, including ipilimumab use in the predocetaxel setting, rilimogene galvacirepvec plus rilimogene glafolivec (PROSTVAC) and granulocyte-macrophage colony-stimulating factor before doce­taxel in asymptomatic ­patients with CRPC, the novel immunomodulator tasquinimod (also in the predocetaxel setting), and novel hormonal therapies such as orteronel.

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