New Standard in Metastatic Prostate Cancer Hits Prime Time

Amy Karon, MPH
Published: Tuesday, Sep 19, 2017
Nicholas J. Vogelzang, MD
Nicholas J. Vogelzang, MD
Although there have improvements in the treatment of men with prostate cancer during the past 15 years, patients with advanced disease continue to pose a clinical challenge. Prostate cancer remains the third leading cause of cancer death among men,1 with more than 26,700 deaths likely to occur in the United States this year.2 Additionally, the incidence of metastatic prostate cancer (mPC), which accounts for 3% of newly diagnosed cases, is rising.3

These statistics reflect more than 7 decades of stagnancy in the treatment of newly diagnosed, hormone-naïve, metastatic disease, researchers say.4,5 Only a few years ago, these patients routinely received androgen-deprivation therapy (ADT) without chemotherapy, which oncologists reserved for ADT failure.6

That picture started to change when the results of the CHAARTED (E3805) trial, first reported at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that adding docetaxel to ADT extended overall survival (OS) by a median of 13.6 months compared with ADT alone.7

That type of OS benefit had “never been seen in metastatic prostate cancer trials and is rarely seen in clinical trials for metastatic solid malignancies,” Voskoboynik and colleagues observed.8 Prior to CHAARTED, researchers seeking to improve outcomes in mPC considered a 2- or 3-month survival benefit noteworthy.9 CHAARTED more than quadrupled that benchmark and spurred strong interest in using chemotherapy earlier, before mPC becomes castration resistant.8 The multiarm STAMPEDE trial confirmed that dual therapy with docetaxel and ADT extended OS by 15 months compared with ADT alone in men with metastatic hormone-naïve (hormone-sensitive) prostate cancer,10 a result that researchers have called “remarkable.”11

Now another set of clinical trial findings, reported at the 2017 ASCO Annual Meeting, is shaking up the treatment paradigm with the prospect of dramatic gains without chemotherapy in advanced disease settings (Table).

 

Table. Practice-Changing Research in Prostate Cancer Trials

Research in Prostate Cancer Trials
Additional survival analyses from STAMPEDE and the results of the LATITUDE trial showed that ADT plus abiraterone acetate (Zytiga), a next-generation adrenal inhibitor, appeared to match or exceed the benefit of ADT plus docetaxel in the metastatic setting. In STAMPEDE, adding abiraterone and prednisolone to ADT lowered the risk of death by about 37% (HR, 0.63; P <.001), cut the chances of treatment failure by about 70% (HR, 0.30; P <.001), and approximately halved the likelihood of serious bone complications compared with ADT monotherapy in men newly diagnosed, locally advanced or mPC.12 In LATITUDE, adding abiraterone and prednisone to ADT lowered the risk of death by 38% (HR, 0.62; P <.001) and significantly improved progression-free survival (HR, 0.5; P <.001) compared with ADT only in men with metastatic castration-sensitive disease.4,13

But even definitive results from large welldesigned clinical trials do not necessarily transform practices quickly, easily, or uniformly. Physicians and patients might be slow to adopt new regimens and treatments for a variety of reasons, including discomfort with change, questions about trial design and generalizability, or concerns about costs, adherence, safety, or tolerability.14

Have the findings from CHAARTED, STAMPEDE, and LATITUDE changed practice? How might they do so in the future, and which questions and controversies remain? Several prostate cancer experts discussed these questions in interviews with OncologyLive®.

A New, Earlier Standard of Care

For newly diagnosed, hormone-naïve prostate cancer, the results of these 3 clinical trials truly are practice changing, experts said. Physicians who conventionally treated advanced prostate cancer with leuprolide or bicalutamide “are really beginning to see the light,” said Nicholas Vogelzang, MD, a medical oncologist at Comprehensive Cancer Centers of Nevada in Las Vegas. “They’re well on the path now to saying that these patients need input from medical oncology.”


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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