Study Could Resolve Abiraterone/Docetaxel Debate in Hormone-Sensitive Prostate Cancer

Andy Hahn, MD

An ongoing phase III study could answer the question of whether abiraterone acetate (Zytiga) added to docetaxel is more effective for patients with metastatic hormone-sensitive prostate cancer than treating patients without the androgen receptor (AR) inhibitor.

The multicenter, multi-arm PEACE1 trial is studying the benefit of docetaxel plus androgen deprivation therapy (ADT), with or without abiraterone and prednisone, and with or without radiotherapy (NCT01957436). The study has an estimated enrollment of 1168 patients and an estimated primary completion date of October 2018.

Prior studies have shown similar outcomes with abiraterone and docetaxel separately in this patient population. Results from the phase III STAMPEDE trial, for example, showed that the addition of abiraterone/prednisone to standard ADT lowered the relative risk of death by 37% and improved progression-free survival (PFS) by 71% compared with ADT alone.¹

The CHAARTED trial investigated docetaxel plus ADT versus ADT alone in patients with metastatic hormone-sensitive prostate cancer. After a median follow-up of 28.9 months, the median overall survival was 57.6 months with ADT plus docetaxel versus 44.0 months with ADT alone (HR, 0.61; 95% CI, 0.47-0.80; P <.001).²

OncLive: What recent advances in metastatic prostate cancer are you most excited about?

Can you expand on darolutamide?

The debate between abiraterone and docetaxel has been ongoing in prostate cancer for quite some time. Can you discuss the conversations physicians continue to have with these agents?

In an interview during the 2018 OncLive^® State of the Science Summit^TM on Genitourinary Cancers, Andy Hahn, MD, a resident at the University of Utah School of Medicine, discussed the ongoing debate between abiraterone and docetaxel and the optimal patient selection for each agent in patients with metastatic hormone-sensitive prostate cancer.Hahn: The most recent advance that I am really excited about is the changing treatment landscape for metastatic hormone-sensitive prostate cancer. You have the introduction of both abiraterone as well as docetaxel within the past couple of years, which has really increased the number of treatment options available to providers. Also, in the next few years, we anticipate that clinical trials are going to read out for apalutamide (Erleada), darolutamide, and enzalutamide (Xtandi), in addition to ADT. There will be a number of new treatment options available for providers and it will be an interesting discussion to see how we tailor treatment.Darolutamide, known as ODM-201, is essentially another novel antiandrogen—it’s an AR antagonist. Additionally, it is in a phase III clinical trial with ADT.There is no true planned randomized clinical trial that has been reported out with ADT plus abiraterone versus ADT plus docetaxel. However, to date, we have one trial that reported out at simultaneous times, where patients were randomized to ADT plus abiraterone versus ADT plus docetaxel—that was the STAMPEDE trial. Between 2011 and 2013, they were randomizing patients to both arms and they reported in the last year that, when you’re comparing abiraterone to docetaxel, they saw no significant difference in overall survival or metastasis-free survival.

What patient or disease characteristics or comorbidities help you choose between one treatment versus the other?

They did see a difference favoring abiraterone for PFS and failure-free survival, but those are surrogate endpoints. In the primary endpoints, there was no difference. It is still being individualized to patients that you’re dealing with. In 2020, what is anticipated to read out is PEACE1, which is being done in Europe. In that clinical trial, there is going to be a direct comparison with planned power to answer the question, “Is one better than the other? Is abiraterone plus ADT or docetaxel plus ADT better?”There definitely are characteristics that would qualify patients more for abiraterone than docetaxel. For abiraterone, you’re thinking [it is more appropriate] for older patients, those with poor performance status, and also patients with low-volume disease—which is defined differently in different cohorts, but not visceral metastases, but at least 5 boney metastases. The actual trials looked at less than 3 boney metastases. However, abiraterone we know probably works well in that group, as well.

In contrast, docetaxel [is better] in younger patients, patients with really good performance status, and then those with high-volume disease. Both in CHAARTED and in another trial, they found that patients with low-volume disease did not benefit from docetaxel; only those with high-volume disease did. Only patients with high-volume disease should be offered docetaxel. Docetaxel has a number of significant toxicities that should limit who is offered it; patients with significant peripheral neuropathy, those who would have trouble with myelosuppression, or who are at an increased risk of infection from other comorbidities probably should not be offered docetaxel because it will cause all of these side effects.

Are there any patients for whom neither agent is an option?

Another kind of comparison between abiraterone and docetaxel is that patients on abiraterone, from the time they start ADT until the time they progress to castration-resistant prostate cancer, they will need to take abiraterone daily with that. With docetaxel, you’re going to get ADT plus docetaxel for about the first 4 months of treatment and then you’ll just continue ADT from that point out. Therefore, if patients are desiring a shorter time of treatment with the additional agent, docetaxel could be better for that cohort.The answer is probably still “yes” to that. With elderly patients who strongly state and desire that they have an interest in being treated but [can handle little] toxicity—and abiraterone and docetaxel both have additional toxicities with treatment—ADT alone would be an option for [that patient cohort]. However, in younger patients with really good performance status who are really looking to prolong life as long as possible, you would want to offer one of those 2 agents to them.

References

1. James ND, DeBono JS, Spears MR, et al. Adding abiraterone for men with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): Survival results from STAMPEDE (NCT00268476). J Clin Oncol. 2017;35 (suppl; abstr LBA5003).
2. Sweeney C, Chen Y, Carducci M. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737-746. doi: 10.1056/NEJMoa1503747.