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Sequencing Questions Remain in Prostate Cancer Paradigm

Danielle Bucco
Published: Tuesday, Feb 13, 2018

Christopher J. Sweeney, MBBS
Christopher J. Sweeney, MBBS
The FDA recently expanded the approval of abiraterone acetate (Zytiga) to include the treatment of patients with metastatic high-risk castration-sensitive prostate cancer, based on findings from the phase III LATITUDE trial.

In the study, 1199 patients were randomized to receive androgen-deprivation therapy (ADT) plus either abiraterone/prednisone or placebo. There was a 38% reduction in the risk of death with the addition of abiraterone and prednisone to ADT compared with ADT alone. After a median follow-up of 30.4 months, the median overall survival was not yet reached with abiraterone acetate versus 34.7 months with placebo (HR, 0.62; P <.001).

In an interview with OncLive, Christopher Sweeney, MBBS, a medical oncologist at Dana-Farber Cancer Institute, discussed the role of abiraterone for patients with hormone-sensitive prostate cancer, and what physicians should consider when choosing between abiraterone and docetaxel.

OncLive: How do you determine whether to administer docetaxel or abiraterone to patients with prostate cancer?

Sweeney: Determining between abiraterone and docetaxel is a challenge, as both drugs work well. Abiraterone is an easier drug for most patients to tolerate because it is a hormonal therapy. Docetaxel also has activity, but it has a higher treatment burden.

Abiraterone is a pill you take daily for many months but has some long-term side effects, such as rising blood pressure. Docetaxel is given for 6 cycles every 3 weeks, but has the common side effects of chemotherapy such as fatigue, weakness, risk of lowering the white cell counts, and neutropenic fever.

Which drug you go with is a topic of big discussion in the community. Once a person progresses, you tend to alternate to the other agent. The other big question here is the cost of these therapies. Docetaxel for a course of 6 cycles is close to $10,000, whereas for 1 month of therapy with abiraterone, it is about $8000. If you are on abiraterone for 3 years, the final cost will depend upon the patient’s copays and out-of-pocket expenses. It is a very complicated financial proposition that may arise when you discuss it with patients, especially when it is over a 3-year period, which is the average amount of time that patients were on abiraterone when they started with hormonal therapy. 

If you start with docetaxel and put the patient on a treatment break and the prostate-specific antigen starts to rise, you can add abiraterone. The patient may only be on it for an average of 18 months, which is half the time of when you would start abiraterone upfront. It is a complicated conversation with balancing treatment burden, the ability to receive docetaxel, and the cost of therapy to the institutions and patients.

Either option is appropriate, but it is important to tailor the decision to the patient’s situation, their financial and physical capabilities, and preference.

How big of a factor is financial burden when you are making treatment decisions?

It is a complicated conversation. I will write the prescription and send it to the pharmacy who will determine if it needs an approval. Then, it will go to the billing department, which will determine a patient’s out-of-pocket expenses depending on their coverage. Some patients have no insurance or have no viability of being able to access it. Most of these patients are on Medicare. Their first bill may be something like $10,000, and the cost is much less once they are past that. It is a complicated conversation that often takes a couple of weeks to resolve.

Which drug is given more frequently?

This is the subject of many conversations and debates around the world. The fashionable answer is the drug that has the lower treatment burden, abiraterone, is given more. It is a simple hormonal therapy and most patients would be able to tolerate it better than docetaxel. It is easier to give when you think about it from a short-term toxicity perspective. However, we may need to sit back and ask, “What is the bigger and more profitable long-term plan?”

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