Figure 1-Current options in metastatic prostate cancer:
Recently, there is randomized prospective data comparing various treatments in metastatic CRPC patients. One example is a study comparing cabazitaxel to abiraterone or enzalutamide in metastatic CRPC patients (study design shown in figure 2). The results of this prospective randomized trial demonstrated a clear benefit to the cabazitaxel arm, as seen in table 1.1 This is also seen when comparing the overall survival rate (Figure 3).
Figure 2 – Randomized prospective study comparing Cabazitaxel to abiraterone/enzalutamide in metastatic castrate-resistant prostate cancer:
Table 1- Clinical benefit rate:
Figure 3 – Overall survival comparing Cabazitaxel to abiraterone/enzalutamide:
There are also new and emerging data regarding cross-resistance between Abiraterone and Enzalutamide. Studies have shown that there is a poor response to enzalutamide if the patient progresses on abiraterone 2,3 and conversely, there is a poor response to abiraterone if the patient progresses on enzalutamide. (4) However, prior androgen receptor antagonist therapy does not affect the efficacy of cabazitaxel. This was demonstrated in a study of 114 patients treated with cabazitaxel in the post-docetaxel setting. Out of the 114 patients, 44 patients received prior abiraterone or enzalutamide, and 70 patients received no prior therapy with either abiraterone or enzalutamide.5 The results showed that with prior therapy the PSA response rate was 34%, and with no prior therapy, the PSA response rate was 40% (figure 4), meaning that no significant difference could be discerned.
Figure 4: Comparison of PSA response rate to Cabazitaxel between prior abiraterone/enzalutamide therapy and no prior therapy:
Delving deeper into similar data from studies assessing the response rate of patients with the androgen receptor splice variant 7 (AR-V7), it is clearly seen that there is a significantly decreased response to enzalutamide and abiraterone, in these specific patients (figure 5).
Figure 5- Decreased response rate to abiraterone and enzalutamide in patients with AR-V7 mutations:
Concluding his talk, Dr. Van Soest stated that there is currently randomized head to head comparisons in the setting of CRPC. These comparisons show that cabazitaxel might be superior to abiraterone or enzalutamide in patients with poor prognosis. Furthermore, there is now data showing cross-resistance between abiraterone and enzalutamide, while cabazitaxel shows no cross-resistance. In any case, biomarkers to help us predict which patients will do better with each specific treatment are the future, and studies investigating these biomarkers should be enhanced.
Presented by: Robert Van Soest, MD, Ph.D., Erasmus MC, Department of Urology, Rotterdam, the Netherlands
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.
References:
1. Chi K et al. Ann Oncol 2018
2. Schrader A et al. Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone. Eur Urol. 2014 Jan;65(1):30-6. doi: 10.1016/j.eururo.2013.06.042. Epub 2013 Jul 2.Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone. Eur Urol. 2014 Jan;65(1):30-6. doi: 10.1016/j.eururo.2013.06.042. Epub 2013 Jul 2.
3. Bianchini D et al. Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone. Eur J Cancer. 2014 Jan;50(1):78-84. doi: 10.1016/j.ejca.2013.08.020. Epub 2013 Sep 25.
4. Attard G et al. Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment. Journal of Clinical Oncology 2018 36:25, 2639-2646
5. Van Soest et al. The influence of prior novel androgen receptor targeted therapy on the efficacy of cabazitaxel in men with metastatic castration-resistant prostate cancer. Eur J Cancer. 2015 Nov;51(17):2562-9. doi: 10.1016/j.ejca.2015.07.037. Epub 2015 Aug 13.