William Oh, MD
The management of metastatic hormone-sensitive prostate cancer continues to evolve as new findings emerge, such as results from the LATITUDE and CHAARTED studies.
The FDA based its recent approval of abiraterone acetate (Zytiga) and prednisone in metastatic high-risk castration-sensitive disease on results from LATITUDE. After a median follow-up of 30.4 months, the median overall survival (OS) was not reached in the abiraterone/prednisone plus androgen-deprivation therapy (ADT) versus 34.7 months with ADT plus placebo (HR, 0.62; 95% CI, 0.51-0.76; P
In CHAARTED patients were randomized to ADT alone or ADT plus docetaxel. After a median follow-up of 28.9 months, the median OS was 13.6 months longer with ADT plus docetaxel versus ADT alone, at 57.6 versus 44.0 months (HR, 0.61; 95% CI, 0.47-0.80; P
In an interview with OncLive
, William K. Oh, MD, chief, Division of Hematology and Medical Oncology, professor, Medicine and Urology, Mount Sinai School of Medicine, associate director, Clinical Research, The Tisch Cancer Institute, discussed treatment with abiraterone versus docetaxel in patients with prostate cancer, other remaining questions in the field, and what role immunotherapy is poised to play.
OncLive: What questions surround abiraterone versus docetaxel in the treatment in prostate cancer?
One of the biggest developments in the treatment of advanced prostate cancer over the past several years has been the management of metastatic hormone-sensitive prostate cancer. This is primarily in patients who are newly diagnosed. In 2014, a plenary session at the ASCO Annual Meeting presented the results of CHAARTED. The results, favoring the use of early chemotherapy, were subsequently published in the New England Journal of Medicine
. A second study, STAMPEDE, confirmed those findings. At that time, we started using docetaxel in the treatment of newly diagnosed metastatic disease.
At the 2017 ASCO Annual Meeting, LATITUDE was presented at the plenary session. LATITUDE was another large, randomized trial of ADT plus or minus abiraterone and showed an extremely comparable benefit for up to 2 to 3 years of abiraterone plus prednisone in the treatment of metastatic hormone-sensitive prostate cancer. An arm of STAMPEDE looked at abiraterone compared with ADT alone and also showed a similar benefit. Now, we have 4 clinical trials that show either docetaxel or abiraterone compared with ADT alone significantly improve survival. The big question remains: which is better?
How do you approach treatment for these patients?
My practice, like in most practices, adapts new therapies as they come about. In 2014, I administered docetaxel after the data were released. However, the challenge after that study was determining whether one or both treatments should be used. Patients have difficulty understanding the nuances of these questions, but they do have their own preferences. Most patients, if given a choice, may prefer not to have chemotherapy.
However, I have had some patients prefer chemotherapy because the treatment, administered 6 times, is over in about 4.5 months. Though a patient may choose abiraterone, it may not be financially feasible for them either because their insurance does not [cover] it, or because the copay can be too expensive. You have to look at the individual characteristics of the patient and incorporate their personal preferences before deciding which treatment best suits them. For most patients, abiraterone has become a more popular choice because it’s an oral therapy and may have a more favorable side effect profile.
What about treatment with enzalutamide (Xtandi)?
Enzalutamide hasn’t been studied in this situation yet. In theory, enzalutamide and abiraterone work similarly mechanistically, so it shouldn't necessarily be any different. It just hasn’t been studied in a large, randomized trial in this setting. There are ongoing studies, and it may have the exact same benefit, but we don't know as of now.
Are there any other settings looking at either abiraterone or docetaxel that might make a clearer distinction between the 2 agents?
The use of abiraterone and docetaxel was established in metastatic castration-resistant prostate cancer (mCRPC). Even in that setting, there are a lot of conversations about both combinations. Should we combine them if they both work and are mechanistically different? Is there an optimal sequence? Is abiraterone followed by docetaxel or docetaxel followed by abiraterone any better or worse?