Is ADT Necessary When You Take Abiraterone Acetate (Zytiga)?
Since the approval of second-generation LHRH Therapies like abiraterone acetate, also known as Zytiga plus prednisone, many men we talk with at Cancer ABCs have asked us if it is necessary to continue taking first-line ADT or hormone therapy along with Zytiga?
Hormone therapy, ADT, causes castration or the removal the androgens such as testosterone from the body. With chemical castration comes many significant and adverse side effects.
These side effects can include loss of libido; loss of muscle; loss of bone mass, causing an increased risk of fractures; hot flashes; cardiovascular complications; mind fog; metabolic complications like diabetes. Given the host of ADT's potential adverse complications, the question is, can stopping ADT improve the quality of life while not compromising the prostate cancer treatment?
In an abstract, 5046, that was presented at the 2019 Virtual ASCO Meeting this question was asked. The abstract provided us with a summation from the SPARE-trial (NCT02077634). SPARE asked, What would happen if men with metastatic castrate resistant prostate cancer who were taking Zytiga and prednisone stopped taking hormone therapy or ADT?
The SPARE-trial was an exploratory phase II study, which included only 67 men. The subject men were randomized to receive either ADT plus Zytiga and prednisone (which was known as Arm A) or Zytiga plus prednisone alone or without ADT (this was know as Arm B).
The goal of SPARE was to determine the value of continuing ADT along with Zytiga and prednisone. The trial’s primary endpoint, or the method they were proposing to answer this question, do men need to continue taking ADT while they also take Zytiga and prednisone, was to measured their radiographic progression-free survival at one (1) year.
Radiographic progression-free survival means that the researchers looked for changes on scans from the trial onset.
The trial showed that there were no difference in the radiographic progression-free survival between the two groups, arm A and arm B.
The trial also showed that the time to PSA progression at one (1) year was not significantly different between the two arms.
However, the researchers did find that in all men who received all three drugs, that’s Zytiga plus prednisone, and ADT, their median testosterone levels remained below castrate levels throughout their treatment protocol. However, in 18% of the men who only took Zytiga and prednisone (that means they did not take ADT), their testosterone levels increased above castrate levels within 28 days after their ADT treatment was stopped.
The researchers concluded, that ADT might not be necessary for men receiving Zytiga and prednisone. However, some men may experience a rapid increase in serum testosterone levels, which warrants close monitoring and adding back ADT if you become non-castrate, or your testosterone levels increase.
SPARE only evaluated the possibility of halting ADT while taking Zytiga and prednisone. It did not consider stopping ADT with any other of the second-generation hormone manipulations like Xtandi or Darolutamide.
This research is not conclusive. It was a very small study and it needs to be replicated at a larger scale before we can have any confidence as to the results.
This study did not evaluate survival differences between the men who stopped ADT and those who continued ADT while they were on Zytiga and Prednisone, it did evaluate radiographic progression, as well as PSA progression, but it did not evaluate survival differences.
It also did not evaluate survival differences; the differences the men experienced in their quality of life or the differences in the two arms' economic costs.
CAUTION
Under no circumstances should you stop your primary ADT treatment without a careful conversation and your medical oncologist's as well as obtaining your oncologist’s agreement to stop ADT.
Suppose you, along with your oncologist, decide to stop ADT while taking Zytiga and prednisone. In that case, you and your doctor must develop and execute a plan to AGGRESSIVELY AND CONTINUOUSLY monitor your serum testosterone levels making sure that you go back on ADT if your “T” levels or testosterone levels rise.