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. It comes with many significant and adverse side effects. These side effects can include loss of libido, loss of muscle, and bone mass, causing an increased risk of fractures, hot flashes, cardiovascular complications, metabolic complications like diabetes, etc. Given the host of ADT's potential adverse complications, can stopping ADT improve the quality of life while not compromising the prostate cancer treatment?
In an abstract, 5046, presented at the 2019 Virtual ASCO Meeting, this very question was asked. The abstract provided us with a summation from the SPARE-trial (NCT02077634); 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 67 men. In the trial, the subject men were randomized to receive ADT plus Zytiga and prednisone (Arm A) or Zytiga plus prednisone alone (Arm B) (no ADT). The goal was to determine the value of continuing ADT to be measured by the primary endpoint of evaluating their radiographic progression-free survival (rPFS) at one (1) year.
The time to PSA progression was 9.6 months in Arm A and 11.2 months in Arm B – these are similar to COUGAR 302, where the median time to PSA progression was 11.1 months. The time to PSA progression or rate of radiologic progression free survival (rPFS) at one (1) year was not significantly different between the two arms.
The researchers found that in all men who received all three drugs, Zytiga plus prednisone, and ADT, their median testosterone levels remained below castrate levels throughout their treatment. In 18% of the men who only received Zytiga and prednisone (no 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.
This research is not conclusive and 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.
It also was a small study that needs to be replicated at a larger scale. This study did not evaluate survival differences between the men who stopped ADT and those who continued ADT while on Zytiga and Prednisone.
It also did not evaluate 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 agreement.
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.
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