Prostate Cancer Studies Made Their Mark at ASCO 2017

According to two studies that made their mark at ASCO 2017, adding Abiraterone acetate (Zytiga) to initial treatment for advanced prostate cancer substantially reduces cancer-related mortality risk.

Prostate cancer is the most common male cancer worldwide. Although incidence is increasing with early screening methods and longer lifespans, prostate cancer mortality is very low. Newly developed treatments contribute greatly to this.

Prostate cancer arises from uncontrolled growth of cells in the prostate gland, a male reproductive gland. Prostate cancer cells need male hormones called androgens—testosterone—to grow. Discovery in the 1940s that their growth and spread depend on hormonal stimulation, followed by the introduction of androgen-suppressing treatments, laid the foundation for metastatic prostate cancer treatment.

Although androgen-suppressing treatments suppress testosterone production, testosterone and other male hormones continue to be produced in the body and tumor. Abiraterone (brand name Zytiga) was developed to suppress this pathway too. It inhibits the enzyme CYP17, which converts other hormones in the body into male hormones. Abiraterone, discovered in 1990 , entered clinical trials for metastatic prostate cancer in 2004. Zytiga (Abiraterone) received approval for advanced prostate cancer previously treated first with conventional androgen suppression, followed by chemotherapy after nonresponse, and progressing under these treatments; in 2011, FDA approval brought it into clinical use. It is still used as 3rd-line treatment in our country.

A major recent question has been whether adding Abiraterone to conventional hormonal therapy benefits regionally advanced and metastatic disease. Another important question concerns advanced patients with high tumor burden, for whom we have used chemotherapy alongside conventional hormonal therapy for 2 years. Could dual hormonal treatment eliminate the need for chemotherapy at this stage? In other words, could initial dual hormonal treatment offer convincing success?

At the American Cancer Congress (ASCO), two presentations on the first day provided substantial answers to these important questions.

The first presented study, STAMPEDE, was also the first to examine Abiraterone’s efficacy as initial treatment.

The study included 2000 patients with both regionally advanced (inoperable) and metastatic prostate cancer. Of these, %48 had regionally advanced disease. Those with regional lymph node involvement received radiotherapy as well as standard treatment. Adding Abiraterone acetate (Zytiga) to initial treatment for advanced, high-risk prostate cancer reduced cancer-related death risk by %37.

At 3 years, survival was %76 with conventional hormonal therapy and %83 when Abiraterone was added. Side-effect rates were similar, although serious side effects were more frequent in the Abiraterone group.

The other Abiraterone study was LATITUDE; adding Abiraterone to conventional hormone suppression in newly diagnosed, high-risk metastatic prostate cancer reduced disease-related death risk by %38.

The phase III study enrolled 1200 patients with at least two risk factors: Gleason 8 or higher, more than three bone metastasis sites , or spread to more than three internal organs.

In high-risk metastatic prostate cancer, adding Abiraterone to standard hormone suppression doubled time to disease worsening (14.3 versus 33 months) and reduced disease-related death risk by %38. Mean overall survival was 34 months with standard treatment, while it could not yet be determined in the Abiraterone arm because many patients were still alive. Abiraterone produced a %53 lower risk of worsening and an additional 18-month delay in cancer growth. Serious side effects were more frequent but were not found unmanageable.

Both studies’ original articles were published in the respected New England Journal of Medicine (NEJM) on the day they were presented.

Previous studies showed that a group of newly diagnosed prostate cancer patients benefits from adding Docetaxel chemotherapy to standard hormone suppression. Both studies showed similar benefit with Abiraterone.

These results are welcome news for prostate cancer patients. New hope has been added to hormonal treatment, which had followed a similar strategy since almost the 1950s. This approach may also eliminate the need for chemotherapy used initially.

Innovations in prostate cancer over the last 10 years have reached dizzying levels, with new treatment options reducing deaths and extending survival remarkably. However, these benefits bring financial difficulties for countries. We hope that, based on equity in health, these innovations will become equally accessible to citizens not only of our country but worldwide.

Comments That Resonated Worldwide

Dr. Richard Schilsky predicts these data will pave the way for Abiraterone’s 1st-line use. Currently it is approved after androgen deprivation therapy (ADT) fails. New data, however, show important benefit when used earlier with ADT.

Another ASCO expert, Dr. Sumanta Kumar Pal, says: “Abiraterone treatment could remove chemotherapy from the current paradigm.”

Dr. Nicholas James of Queen Elizabeth Hospital in the United Kingdom states that this study has the greatest survival rate reported to date in adult cancers.

Dr. Karim Fizazi, department head at Gustave Roussy Cancer Center, Paris-Sud University, commented: “The benefit of Abiraterone used in the 1st line in this study is comparable with that of docetaxel in previous trials. However, Abiraterone is more comfortable for patients. Many patients reported no side effects. These findings suggest adding Abiraterone and prednisolone (cortisone) to ADT as a new treatment for at-risk patients with newly diagnosed metastatic prostate cancer.”

Dr. Pal explained: “The CHAARTED study a few years ago shook the foundations of previous prostate cancer research. Adding chemotherapy to hormone treatment increased survival chances. Comparing existing chemotherapy and Abiraterone data, survival benefit seems similar with both. But chemotherapy causes side effects harder for patients to handle. Abiraterone offers more effective treatment with fewer side effects.”

Dr. Charles Ryan of the University of California, San Francisco, said: “These data are certainly impressive and will undoubtedly improve outcomes for patients with metastatic disease.”

Dr. Matthew R. Zibelman of Hematology and Oncology at Fox Chase Cancer Center in Philadelphia said: “Standard treatment for this group is chemotherapy. We now have another option with fewer side effects for newly diagnosed metastatic hormone-sensitive prostate cancer.”

However, Dr. Otis Brawley of the American Cancer Society cautioned against immediately embracing the results: “Hormone therapy in prostate cancer can cause heart disease. We fear losing patients to treatment-related heart disease. This applies to all hormonal treatments we use in prostate cancer. For me, efficacy and side effects are a double-edged sword. I will use this new approach to treat prostate cancer but will be selective. I will choose not to use it in patients with diabetes or coronary artery disease. I acknowledge the reported data have wonderful aspects, but as doctors we should approach such data more carefully.”