Christopher Sweeney, MBBS, medical oncologist at the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, discusses results of the phase III ENZAMET trial, which looked at standard therapy with or without enzalutamide (Xtandi) as a treatment for patients with metastatic hormone-sensitive prostate cancer.

It is known that in this hormone-sensitive setting that patients also benefit from receiving docetaxel, which was discovered in the CHAARTED trial, Sweeney explains. Therefore, ENZAMET was then amended to include a group of patients who could also receive prior docetaxel, which was approximately 50% of enrolled patients and included mostly those with a high volume of disease. Results showed that enzalutamide prolonged overall survival (OS) in patients with high- and low-volume disease, and a longer time to disease progression. 

Additionally, although early enzalutamide prolonged time to progression in patients who received docetaxel, there was not a significant treatment effect. Those who did not have docetaxel had a clear improvement in time to progression and also in OS, Sweeney concludes.

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Christopher Sweeney, MBBS, medical oncologist at the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, discusses results of the phase III ENZAMET trial, which looked at standard therapy with or without enzalutamide as a treatment for patients with metastatic hormone-sensitive prostate cancer.

Dr. Sweeney on the Phase III ENZAMET Trial in Metastatic Hormone-Sensitive Prostate Cancer

Christopher Sweeney, MBBS, medical oncologist, Dana-Farber Cancer Institute, discusses when to give docetaxel as a treatment option for patients with prostate cancer.

Docetaxel is cheaper than other therapies, explains Sweeney. When the patient is healthiest, that is when they are able to receive docetaxel. The patient is done with the therapy after 6-cycles and then they get put on hormonal therapy. Therefore, they are not at risk of the longer toxicities of abiraterone acetate (Zytiga).

The recent positive findings seen with docetaxel come from 2 randomized trials—CHAARTED and STAMPEDE. In the larger STAMPEDE trial (2962 patients), adding docetaxel to standard hormonal therapy significantly improved survival among men with newly diagnosed, hormone-naïve advanced prostate cancer.

The median overall survival (OS) was 81 months with docetaxel plus standard of care (hormonal therapy with or without radiotherapy) versus 71 months with standard of care alone (0.78; 95% CI, 0.66-0·93; P= .006). In the CHAARTED study (790 patients), the median OS was 57.6 months with the combination of docetaxel and androgen-deprivation therapy (ADT) versus 44 months with ADT alone (HR, 0.61; 95% CI, 0.47-0.80; P <.001).

Dr. Sweeney on Chemotherapy in Prostate Cancer

Christopher Sweeney, MBBS, medical oncologist, Dana-Farber Cancer Institute, discusses tailoring treatment to individual patients with prostate cancer.

A big question regarding the treatment of prostate cancer is the cost of the therapies. For example, 6 cycles of docetaxel—including cost of drug and infusion&mdash;is about $10,000, compared to 1 month of therapy with abiraterone acetate (Zytiga), which is about $8,000. What a patient may pay depends on their copays and out-of-pocket costs. This makes it a very complicated financial proposition, says Sweeney, especially considering patients can be on these therapies for up to 3 years.

This is something that may come up when talking to patient, so tailoring treatment options to the patients is important, explains Sweeney. Either docetaxel or abiraterone is appropriate for patients with metastatic castration-resistant prostate cancer, but factors such as treatment burden, ability to receive the agent, and cost of therapy to the patient and institution, must be taken into account.

Dr. Sweeney Discusses Tailoring Treatment in Prostate Cancer

Christopher Sweeney, MBBS, medical oncologist, Dana-Farber Cancer Institute, discusses the role of chemotherapy versus abiraterone (Zytiga) for patients with metastatic castration-resistant prostate cancer (mCRPC).

Both docetaxel and abiraterone work well, says Sweeney, but the issue is getting both drugs to achieve maximum benefit. Abiraterone is easier to tolerate since it is a hormonal therapy whereas docetaxel has a higher treatment burden.

Combining both regimens with a hormonal therapy shows similar benefit, explains Sweeney, which makes determining which regimen to give first a challenge.

Dr. Sweeney on Chemotherapy Versus Abiraterone for mCRPC

Christopher Sweeney, MBBS, physician, Dana-Farber Cancer Institute, compares treatment with abiraterone acetate (Zytiga) verus docetaxel in patients with prostate cancer.

Both drugs have their pros and cons, according to Sweeney. Abiraterone is an oral agent that must be taken for months at a time. While the side effects may not be as severe, they can be longer lasting than those seen with docetaxel. Adverse effects include high blood pressure and diabetes. Docetaxel, on the other hand, which is administered intravenously, only needs to be given to patients every 3 weeks for 6 cycles. However, the agent comes with typical chemotherapy-related toxicities, such as fatigue and weakness, low white blood cell counts and neutropenic fever.

Deciding between the 2 agents is often difficult for clinicians and their patients, especially since the two have nearly the same efficacy, according to Sweeney. Once a patient progresses or stops responding to one of the treatment, they will often be switched on to another.

Christopher Sweeney, MBBS, physician, Dana-Farber Cancer Institute, compares treatment with abiraterone verus docetaxel in patients with prostate cancer.

Comparing Abiraterone and Docetaxel in Prostate Cancer Treatment

Christopher Sweeney, MBBS, medical oncologist, Dana-Farber Cancer Institute, discusses the future of prostate cancer research.

There have been several drugs approved to treat patients with castration-resistant prostate cancer: abiraterone, enzalutamide, sipuleucel-T, radium-223, and cabazitaxel. The challenge remains to determine proper combinations and sequencing. Sweeney says the oncology community needs to commit to clinical trials to answer these persisting questions.

Sweeney says he is leading a trial looking at hormonal therapy with or without enzalutamide, allowing for upfront docetaxel, in patients with hormone-sensitive disease. Sweeney believes the way forward is to combine drugs in the castration-resistant setting and use combinations earlier in the hormone-sensitive setting.

Christopher Sweeney, MBBS

Articles

Dr. Sweeney on the Phase III ENZAMET Trial in Metastatic Hormone-Sensitive Prostate Cancer

Dr. Sweeney on Chemotherapy in Prostate Cancer

Dr. Sweeney Discusses Tailoring Treatment in Prostate Cancer

Dr. Sweeney on Chemotherapy Versus Abiraterone for mCRPC

Comparing Abiraterone and Docetaxel in Prostate Cancer Treatment

Dr. Sweeney on the Future of Prostate Cancer Research