The trial focuses on men with de novo metastatic prostate cancer, so in other words men who are diagnosed with up front metastases right at the same time they are diagnosed with a prostate cancer. The incidence for that is about 3-5% in most Western countries but now, having said that, if you go to large countries in Asia such as China or India this incidence can rise to up to 60% of men who are diagnosed with prostate cancer. Historically castration or androgen deprivation therapy has been the standard of care and this is because it basically works almost in 100% of patients, at least at the beginning. Having said that, by approximately a year on androgen deprivation therapy about half of these patients with metastatic disease have already developed cancer progression, what we call castration resistance.
Since 2015 ADT plus docetaxel, so a chemotherapy agent, has been the new standard of care for patients with metastatic prostate and at least those with a high metastatic burden, thanks to three trials including one presented and published by Dr James. In LATITUDE we actually evaluated the role of abiraterone plus prednisone on top of androgen deprivation therapy in these patients with high risk metastatic disease. This is because abiraterone is already an agent we’re using in patients with castration resistant disease; it’s active, it’s approved and it’s associated with improved overall survival.
This is the design of the trial, it’s a straightforward comparison of androgen deprivation therapy alone or with a placebo or the same plus abiraterone 1g/day plus prednisone 5mg/day. Two co-primary endpoints: radiographic progression free survival and overall survival. This was a global trial, a very large trial, and docetaxel was not used in the standard of care just because the trial was designed and it fully enrolled its planned accrual before the data supporting the role of docetaxel were out.
Here are now the good news. To the left of the slide you will see overall survival and, as you can see, this is a positive phase III trial with a significant improvement in overall survival and a 38% reduction in the risk of death. The hazard ratio is 0.62. If you would like to see the median it’s approximately 35 months in the control arm, so basically what we are expecting, and it’s not even reached in the abiraterone arm which is telling you that really the difference is very important. At three years 66% overall survival rate in the abiraterone arm versus 49% in the control arm.
To the right is radiographic progression free survival, the other co-primary endpoint. Here again you see that abiraterone is associated with a significant improvement and a 53% risk reduction. Medians of 14.8 months in the control arm versus 33 months in the abiraterone arm, so more than twice improved. This good news didn’t come alone and actually all secondary endpoints were also met: time to PSA progression, suffering from PSA progression is associated with anxiety in these men, time to pain progression, time to next symptomatic skeletal event such as fractures etc., time to chemotherapy, time to subsequent prostate cancer therapy.
Now, in terms of safety we basically show what we already knew from abiraterone safety patterns including an excess in hypertension and hypokalaemia, a slight transaminase increase, which is most of the time asymptomatic, and also a slight increase in cardiac disorders, so this is really what we already knew from this compound when we’re using it in the castration resistant setting.
In conclusion, in LATITUDE, which was a phase III trial conducted in men with high risk de novo metastatic disease, adding abiraterone plus prednisone to standard of care with castration significantly improved overall survival with a 38% reduction in the risk of death and also a significant improvement in radiographic progression survival, 53% reduction in the risk of death or progression. All secondary endpoints were met. The safety profile was that we already knew with this compound in the castration resistant setting and, in my opinion, this finding supports the fact that adding abiraterone and prednisone to castration should now be considered as the new standard of care for these men with high risk newly diagnosed metastatic prostate cancer. Thank you very much.