Yu Shares Insight on Recent Advances in Castration-Sensitive Prostate Cancer

Evan Ya-Wen Yu, MD

The prognosis for patients with castration-sensitive prostate cancer continues to improve, with the recent FDA approval of abiraterone acetate (Zytiga), an agent that has shown promising survival signals. Results from the LATITUDE and STAMPEDE trials have contributed to this dramatic shift, said Evan Ya-Wen Yu, MD.

Abiraterone was approved in February 2018 for use in combination with prednisone for patients with metastatic highrisk castration-sensitive prostate cancer. This approval was based on findings from the phase III LATITUDE trial, in which the addition of abiraterone and prednisone to androgen deprivation therapy (ADT) demonstrated a 38% reduction in the risk of death compared with ADT alone.¹

The STAMPEDE trial also investigated abiraterone, showing that it lowered the relative risk of death by 37% when added to standard ADT. Additionally, abiraterone improved progressionfree survival by 71% in metastatic and nonmetastatic patients with high-risk hormone-naïve prostate cancer.²

OncLive: Please discuss how treatment has changed for patients with castration-sensitive prostate cancer.

In an interview during the 2018 OncLive^® State of the Science Summit™ on Genitourinary Cancers, Yu, a professor in the Division of Oncology at the University of Washington, and member of the Clinical Research Division at Fred Hutchinson Cancer Research Center, discussed the evolution of treatment for patients with castration-sensitive prostate cancer and how he decides between treatment with abiraterone and docetaxel for this population.Yu: The field has recently changed dramatically after the [results of the] CHAARTED and STAMPEDE trials showed that 6 cycles of docetaxel, when added to standard ADT, led to a dramatic survival benefit for men with newly diagnosed metastatic prostate cancer. There were some patients in the STAMPEDE trial who did not have metastatic disease, but in regard to subsets, we still have to see the long-term benefit. For metastatic disease, it is very cut and dry; there is benefit with docetaxel, especially for those with high-volume disease.

More recently, the LATITUDE and STAMPEDE trials showed that adding abiraterone to ADT also leads to a dramatic survival benefit. This increases the number of choices that one has. We certainly do not know whether abiraterone or docetaxel is better. Personally, I am using abiraterone for my low-volume—disease patients. For high-volume disease, I offer both. I recognize that there are many considerations in regard to the number of doses of docetaxel, duration of therapy of abiraterone, and financial toxicity. All of these things need to come to light.

The other thing regarding treatment intensification is the future of these diseases. There are many clinical trials with combination therapy as well. Additionally, there are many trials that are now thinking about doing metastases-directed therapy, removing oligometastatic disease surgically or with radiation, and also studies looking at removing the primary lesion of the prostate or providing radiation to the prostate. Those trials are underway, and we look forward to seeing the results of that.

What else would you like to highlight from LATITUDE, CHAARTED, and/or STAMPEDE?

What other agents are promising other than abiraterone and docetaxel?

Finally, I spoke about identifying metastases early for patients with biochemical recurrence using next-generation imaging such as prostate-specific membrane antigen-PET to identify early metastases to then do metastases-directed therapy. This is early ongoing research, but it is generating a lot of excitement in the field.If you look across cancer studies, regardless of the malignancy or agents, it is not uncommon to see a 2-, 3-, 4-, or 5-month median survival benefit. With these agents, we are seeing survival benefits in terms of 1 to 2 years in certain subsets. These are incredibly dramatic and convincing data. There is really no doubt about it.There are a lot of studies going on right now that take the same theories—adding chemotherapy earlier. There will be a study coming out looking at cabazitaxel chemotherapy in this setting. There are studies looking at enzalutamide (Xtandi) and apalutamide (Erleada) in this setting, and there are studies that allow combinations of chemotherapy with a second-generation androgen-targeted agent.

What are the factors that you take into consideration when treating a patient with low-volume disease?

Now that we have seen the survival benefit with docetaxel and abiraterone, the question is, “Should we be sequencing them or possibly combining them?” There will be some studies with other related types of agents out there that will sequence and combine these agents. That will teach us the best thing to do in the future.Certainly, comorbidities are always important. Duration of therapy, financial toxicity, and patient comorbidities are all important. Patient side effect profiles are important; certainly, docetaxel has its unique side effect profile with neuropathy, hepatic issues, and some patients needing to take high doses of steroids prior to dosing.

What would you say is the prognosis for castrationsensitive prostate cancer?

Is there anything coming up on the horizon that you would like to mention?

One nice thing is that they don’t have to take chronic steroid dosing. For instance, in metastatic castration-resistant prostate cancer trials, [the regimens] are all accompanied with 5 mg of prednisone twice daily. In the CHAARTED trial, they did not use prednisone. Whereas when you give abiraterone, that might be a consideration for someone who is a brittle diabetic. There are multiple comorbidity associations that may push you one way or another.The prognosis has improved over time. Traditionally, [findings from] older studies in this setting have shown a prognosis ranging from 3.5 years to 5 years. We have not had long-term outcomes, because a lot of these patients from these studies that we are talking about are still alive. A lot of the data that have come out are from interim analyses. Plus, with all of the new drugs available for metastatic castration-resistant prostate cancer (mCRPC), I would be shocked if the prognosis overall wasn’t better.There is a lot of excitement in this area. When it comes to treating patients with castration-sensitive disease, the challenge is trial development. This is actually a good challenge, because the prognosis is good—these patients live for years. But, it takes a long time for the data to mature.

I would say that the more immediate things occurring in the field that will garner a lot of press are the use of immunooncology agents such as PD-1/PD-L1 antibodies and selecting patient populations for that. Also, the introduction of PARP inhibitors for homologous recombination deficient patients. Should we be combining immuno-oncology agents with PARP inhibitors? These are the things that are the most immediate because they are already being tested in patients with mCRPC. We will get to an answer soon.

References

1. Fizazi K, Tran N, Fein LE, et al; LATITUDE Investigators. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352-360. doi: 10.1056/NEJMoa1704174.
2. 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). doi: 10.1200/JCO.2017.35.18_suppl.LBA5003.