Philip W. Kantoff, MD
While immunotherapy continues to make headway in various malignancies, the chemotherapy docetaxel maintains a key role in the treatment of patients with metastatic prostate cancer.
Philip W. Kantoff, MD, lectured on cytotoxic chemotherapy for prostate cancer during the 2016 OncLive
State of the Science Summit on Genitourinary Cancers. He also offered insight on the use of PARP inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) who have DNA damage-repair abnormalities.
In an interview, Kantoff, chairman of Medicine at Memorial Sloan Kettering Cancer Center and a 2014 Giants of Cancer Care winner for Genitourinary Cancer, discusses data supporting the use of docetaxel in metastatic prostate cancer and ongoing studies exploring PARP inhibitors in the field.
OncLive: Please provide an overview of your presentation.
: Docetaxel was approved for use in advanced prostate cancer about 12 years ago as a result of 2 studies, which demonstrated that docetaxel improved overall survival (OS) by about 3 months. That has been the standard of care for advanced mCRPC since that time. There have been a number of studies that have tried to add other agents to docetaxel chemotherapy without any success. Therefore, large randomized studies adding different biological agents to it failed to demonstrate any benefit.
For second-line chemotherapy, cabazitaxel (Jevtana) was approved about 6 years ago. This was the result of a study called TROPIC, in which patients who had been treated previously with docetaxel and had progressed were randomized to receive mitoxantrone chemotherapy, which was a standard palliative agent for the treatment of advanced prostate cancer, or alternatively, 25 mg/m2 of cabazitaxel. In fact, 25 mg of cabazitaxel given every 3 weeks was found to be superior to mitoxantrone chemotherapy and improved survival by several months.
A recent study was performed asking the question, “Could cabazitaxel be used as first-line chemotherapy and what is the appropriate dose of it?” A 3-arm randomized study called FIRSTANA was performed comparing the standard dose of docetaxel at 75 mg/m2 to the standard dose of cabazitaxel 25 mg/m2 or alternatively 20 mg/m2 with cabazitaxel. As it turned out, all 3 arms were exactly the same with regards to PFS and OS. It does not appear that cabazitaxel at either 25 or 20 mg is superior to docetaxel. Docetaxel remains first-line chemotherapy for men with mCRPC.
It turned out 20 mg/m2 and 25 mg/m2 of cabazitaxel were equivalent with regard to outcomes and 20 mg/m2 was less toxic than 25 mg/m2. For the second-line setting, it is perfectly reasonable to use the 20 mg/m2 dose because it is less toxic.
What about docetaxel’s potential in the setting of metastatic hormone-sensitive prostate cancer?
There have been 2 seminal studies that were published in the past couple of years. One is the CHAARTED study and the other is the STAMPEDE study. In these 2 studies, men with advanced hormone-sensitive prostate cancer were randomized to standard of care, which was androgen-deprivation therapy (ADT), or ADT plus 6 cycles of docetaxel. These 2 studies gave remarkable results in that the concomitant use of docetaxel with ADT led to a marked improvement in OS in both studies.
The controversy that now exists is, who are the appropriate patients who should be treated with the combination of ADT and docetaxel? It appears that, based on follow-up from the CHAARTED study, only men with high-volume disease as defined by 4 or more bone metastases and/or visceral metastases were the ones who benefitted from the combination.