ASCO Preview: Cabazitaxel, Survival Surrogate Endpoints in Prostate Cancer

A. Oliver Sartor, MD

Ahead of the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago, we are discussing upcoming prostate cancer data to be presented at the meeting with Oliver Sartor, MD, a medical oncologist who specializes in prostate cancer at the Tulane Cancer Center in New Orleans, Louisiana. Dr. Sartor will be presenting results of the FIRSTANA phase III clinical trial on Monday, June 6 at the meeting. The trial is testing cabazitaxel compared to docetaxel in chemotherapy-naive prostate cancer patients.

- Interviewed by Anna Azvolinsky 

Cancer Network: Let’s start with how cabazitaxel is currently used in patients with prostate cancer.

Dr. Sartor: It’s currently US Food and Drug Administration (FDA)-approved in the second-line chemotherapy setting. So the trial called TROPIC was evaluating cabazitaxel, 25 mg/m² in comparison to mitoxantrone, which was given at 12 mg/m². Both arms, by the way, were inclusive of prednisone. And in that trial, there was an overall survival benefit for patients who had metastatic castration-resistant prostate cancer among those individuals previously treated with docetaxel, so clearly a second-line trial. And that is where the FDA approval is today and that’s how cabazitaxel is being used today.

Cancer Network: Can you tell us about the study design of the FIRSTANA phase III trial and also the rationale for the trial?

Dr. Sartor: It turns out that if cabazitaxel is better than the [standard of care] second-line therapy, and that was proven in TROPIC, the question is how would it compare to first-line therapy. And the first-line chemotherapy is called docetaxel-it’s been FDA-approved since 2004-and so really, the FIRSTANA trial was to compare docetaxel with cabazitaxel. There were two doses, 20 mg/m² and 25 mg/m² looked at for cabazitaxel whereas docetaxel was one dose, 75 mg/m², which is the currently FDA-approved standard.

Cancer Network: Anything as far as the trial design in the context of other first-line therapies that are now approved, abiraterone and enzalutamide?

Dr. Sartor: The way the trial was designed, it was the castration-resistant, chemotherapy-naive patients who were evaluated. So there was the possibility that patients could have been treated with abiraterone or enzalutamide prior to treatment on this trial. It turns out that not many patients actually were treated in that manner. So this is basically a first-line chemotherapy trial with primarily older hormones preceding the chemotherapy.

Cancer Network: Are there other prostate cancer results to be presented at the meeting that you are looking forward to and can highlight?

Dr. Sartor: There is an analysis that is going to look at essentially all the randomized trial done in localized disease and trying to find out whether or not there are some intermediate endpoints that could be utilized to predict overall survival. I think we know that patients who are diagnosed with early-stage disease are not going to die-as a whole-until many years later, and trying to do therapeutic interventions, particularly with novel therapeutic interventions in that space has been compromised. So I think there are going to be new data from the ICECaP Working Group that will be interesting. So that is one thing I am looking forward to in particular.

Another trial I might mention. There has been a lot of discussion about the dose of radiation potentially making hormonal therapy irrelevant for those with localized disease. It’s a nice study from France that will help to evaluate that question using high-dose rates of radiation therapy, moving up to 80 Gy, and then randomizing patients to hormones or no hormones in an attempt to determine whether or not you really need hormones for those individuals treated with high-dose of radiotherapy.

Cancer Network: Are there ongoing trials not yet reported that you and your colleagues are looking forward to reading out in the next few years?

Dr. Sartor: There are a lot of trials that are potentially going to be reading out. I think there is a lot of excitement right now about the PARP inhibitors. There is a very nice New England Journal of Medicine article, published last October, in which there was clear delineation of PARP inhibitors having activity in those with DNA repair defects. And these include things like the BRCA genes and ATM. And there is a move afoot now to be able to explore the BRCA- and ATM-mutant patients with PARP inhibitors in a more definitive fashion. A lot of people are looking forward to that. There are some immunotherapy trials like the PROSTVAC/TRICOM trial that is fully accrued right now that is waiting for read out, that is being done by Bavarian Nordic. That is an overall survival trial. That clearly is going to be an important trial. There are a variety of smaller trials. It’s not ready to read out yet, but will be completed accrual quite soon, of abiraterone plus or minus radium-223. Another trial I think is a good trial is enzalutamide plus or minus abiraterone-currently accruing and accruing very well. So there are some nice trials that we will learn a lot from that we can look forward to.

Cancer Network: Thank you so much for joining us today, Dr. Sartor and enjoy the conference.

Dr. Sartor: Thank you, I appreciate it.