Among the current unmet needs in prostate cancer, the lack of therapeutic options for non-metastatic castration-resistant prostate cancer (nmCRPC) patients and the need to delay the onset of castration-resistant disease in metastatic hormone-naïve prostate cancer (mHNPC) are two of the most pressing ones. There are currently several drugs in Phase III development for the treatment of nmCRPC and mHNPC. Among those, Astellas/Pfizer’s Xtandi (enzalutamide) and Johnson & Johnson’s (J&J’s) Zytiga (abiraterone acetate), which are both already approved for the treatment of metastatic castration resistant prostate cancer (mCRPC), are likely to address the two unmet needs mentioned above.

Based on the 2017 data readouts from two practice-changing studies (LATITUDE and PROSPER), Zytiga and Xtandi showed promising results in mHNPC and nmCRPC, respectively. Results from the LATITUDE study, which investigated the use of Zytiga in combination with the current standard of care (SOC) of androgen deprivation therapy (ADT) in mHNPC, were presented at the 2017 American Society of Clinical Oncology (ASCO) annual meeting. Zytiga + ADT was able to induce a 38% relative improvement in survival and a 71% improvement in failure-free survival compared with ADT alone, representing one of the biggest survival gains reported in a solid tumor to date. The onset of castration-resistant disease was also delayed (33.0 months for Zytiga + ADT versus 14.8 months for ADT alone). More recently, on September 14, Pfizer and Astellas announced positive top-line results from the PROSPER trial, where Xtandi was able to achieve the primary endpoint of metastasis-free survival in nmCRPC.

Zytiga and Xtandi, both of which target the androgen receptor (AR) signalling pathway, currently have a major role in the treatment of mCRPC, an indication for which the two hormonal agents were approved in 2011 and 2012, respectively. The two drugs have contributed significantly to extending the survival of patients who had previously been exclusively treated with the toxic chemotherapy agent, docetaxel. However, the long term efficacy of Zytiga and Xtandi in mCRPC is limited by the appearance of acquired resistance, which occurs after approximately 12 months of treatment. A high degree of cross-resistance between the two drugs is also a major problem and a decisive factor shaping the treatment algorithm of mCRPC, where Zytiga and Xtandi are rarely used subsequently.

Based on the results from LATITUDE and PROSPER, GlobalData expects a high use of J&J and Astellas/Pfizer’s AR-targeted drugs earlier in the disease course of mHNPC and nmCRPC. However, the early exposure and appearance of mechanisms of resistance will limit the use of these hormonal agents in mCRPC patients in the future, once again leaving patients with docetaxel as the only treatment option when the transition to mCRPC occurs. Although the benefits provided by Zytiga and Xtandi in mHNPC and nmCRPC are indisputable and will fulfill two unmet needs, they will also open the way to the development of new unmet needs. GlobalData expects that, in the next few years, the identification and characterisation of new molecular targets and targeted agents exploiting new mechanisms of action, as well as the discovery of predictive biomarkers for mCRPC, will become two of the major unmet needs in the prostate cancer space.