The Shifting Sands of the Prostate Cancer Treatment Landscape
By Mara Jeffress, Ph.D., Associate Consultant, Kantar Health
Advances in the treatment of metastatic castrate-resistant prostate cancer (mCRPC) have expanded recently. For years the only treatment option was docetaxel plus prednisone, but five new options have been approved in the past four years, with more agents on the horizon. Currently, patients may be eligible to receive docetaxel, Zytiga® (Johnson & Johnson/Janssen), Provenge® (Dendreon), or Xofigo® (Bayer) as first-line therapy for mCRPC. In patients previously treated with docetaxel additional treatment options are Xtandi® (Astellas/Medivation) or Jevtana® (Sanofi). What used to be a disease with only one effective option now can be managed through multiple lines of therapy.
With so many options, how do physicians decide which agents to use first? U.S. oncologists suggest that symptomology plays a significant role in the decision. Several years ago, asymptomatic or mildly symptomatic patients might not have been treated but rather observed until symptoms or disease progressed to the point to justify the use of toxic chemotherapy. Now, however, the approval of effective and well-tolerated agents has made early treatment of mCRPC more common.
Asymptomatic or mildly symptomatic patients are likely to receive Zytiga or, less commonly, Provenge. Zytiga may also be used in symptomatic patients, although the presence of highly symptomatic disease is more likely to drive a choice of docetaxel (if the patient is fit enough to receive chemotherapy). While Xofigo can be given in the front line to symptomatic patients with bone metastases, it is usually reserved for later lines.
Across all patient types and symptomologies, docetaxel was the standard of care in the front line, but with the recent line extension for Zytiga into the chemo-naïve setting, the landscape is changing rapidly. In front-line treatment, Zytiga now surpasses docetaxel across the broad range of mCRPC patients in the U.S. (see Figure 2). The trend in Western Europe (data not shown) is moving in the same direction.
Near-Term Impact of the Front-Line Paradigm Shift
Zytiga and Xtandi were both launched in the post-docetaxel setting. As mentioned, Zytiga has since received additional approval for use in the chemo-naïve setting, and Xtandi is also expected to be approved in this setting shortly (FDA PDUFA date of September 18, 2014). The movement of these next-generation hormonal agents into the chemo-naïve setting has resulted in the taxanes – previously the first-line standard of care – now being relegated to later lines in the majority of patients, likely due to their harsher toxicity profiles. As shown in Figures 2-4, docetaxel and Jevtana now have their highest share in third-line mCRPC. The treatment paradigm may further change and grow more complicated with the anticipated approval of Xtandi in front line; notably, it has already received a category 2A recommendation for first-line use by the National Comprehensive Cancer Network (NCCN).