Addition of cabazitaxel to abiraterone/prednisone significantly prolonged PFS in extensive disease following docetaxel

Dr Christos Kyriakopoulos - University of Wisconsin Carbone Cancer Center, Madison, USA

Yesterday I had the pleasure to present the results of the CHAARTED2 study. It’s ECOG-ACRIN 8153, a cooperative group study, that examined the role of adding cabazitaxel to abiraterone for patients who have developed castration resistant disease after receiving docetaxel plus androgen deprivation for metastatic castration sensitive prostate cancer. The study is a randomised phase II study.

We enrolled 223 patients randomised to two arms. Patients in arm A received cabazitaxel 25mg/m2 for up to six cycles plus standard dose abiraterone and prednisone. Patients in arm B, which was the control arm, received treatment with standard dose abiraterone and prednisone alone. The study showed a progression free survival benefit of 5 months in favour of the patients who received cabazitaxel with a hazard ratio of 0.73 and a p-value of 0.049 so it’s a positive study.

Other endpoints included in the analysis were also in favour of the group of patients who received cabazitaxel plus abiraterone, like PSA response and time to PSA progression. However, the study did not show an overall survival benefit from the addition of cabazitaxel but still it’s a small study to show that. Probably patients who progressed on abiraterone ended up getting cabazitaxel, it’s an approved drug, or other treatments. So for a study like that it’s difficult to show an overall survival benefit.

The combination of cabazitaxel plus abiraterone was overall well tolerated. We did see some cytopenias which are expected from the use of chemotherapy. Also the grade 3 and 4 side effects related to the treatment are very similar to side effects that have been observed in other studies that included cabazitaxel. So, overall I would say that the regimen was well tolerated. Also about 77% of patients were able to complete all six cycles of chemotherapy, even though about 65% of patients required some treatment modification.

However, the conclusion of the study, even though it’s a positive study, over the last several years there have been a lot of changes in the treatment landscape. The results of the study are not applicable in today’s landscape. This is not something that we can take to clinic today simply because most patients nowadays receive a second generation AR inhibitor, whether it’s abiraterone or something else, in the castration sensitive setting. Also even if they receive chemotherapy, like docetaxel for castration sensitive disease, that will also be in the context of a triplet therapy. So technically with today’s standards patients who progress and develop castration resistant disease have already been exposed to a second generation androgen receptor inhibitor plus/minus chemotherapy. So the results are not very relevant in today’s practice.

Nevertheless, we did confirm that cabazitaxel is active in that setting. We also showed that maybe one of the take-home points from these studies may be an earlier intervention with cabazitaxel in that setting might be beneficial, depending on how patients do on abiraterone alone. This is something that will need to be explored in a future study but there is some evidence supporting that.

Thank you.