A certain treatment can help reduce side effects in prostate cancer by managing testosterone levels.
Among patients with prostate cancer, treatment with the oral hormone-suppressing drug Orgovyx (relugolix) is “basically as good or slightly better at lowering the level of testosterone and keeping the testosterone stably low during the course of treatment” when compared with injectable hormone antagonists Lupron (leuprolide) or Firmagon (degarelix), as one expert explained to CURE®.
Explaining the results of an analysis of 260 patients with prostate cancer receiving radiotherapy and androgen deprivation therapy (ADT) from two randomized clinical trials reported in JAMA Oncology, Dr. Atish Choudhury, a genitourinary medical oncologist and the chair of the Gelb Center for Translational Research at Dana-Farber Cancer Institute in Boston, noted that patients experienced faster testosterone recovery when treated with the oral drug.
“In both studies, what was potentially more interesting was that the recovery of testosterone was faster after stopping the oral drug compared to the two injectable drugs used as the comparators,” Choudhury said. “And so, the side effects of the treatments while people were receiving the drugs was about similar, but we anticipate that a lot of the side effects of the treatment would recover sooner if the testosterone recovers more quickly.”
“Importantly, there was no signal that the oral drug, [Orgovyx], changed the effectiveness of the radiation treatment or led to unanticipated side effects with radiation compared to the injectable drugs that have been used in conjunction with radiation for a long time,” he also noted.
Orgovyx, researchers wrote, “achieved high castration rates in 95% or more of patients across localized, locally advanced, recurrent, and/or metastatic disease. Rapid testosterone recovery was achieved with [Orgovyx], and no new safety concerns were identified in the radiotherapy setting.” These results, they further noted, “suggest that [Orgovyx] is safe and effective in patients receiving radiotherapy for prostate cancer.”
The injectable treatments, Choudhury explained, work by initially overloading the body’s testosterone production machinery, leading to an overdrive of the system that eventually causes it to shut itself off. Orgovyx, conversely, directly blocks the production of testosterone.
“So, rather than overdriving the system and then locking it up, [Orgovyx] actually locks it directly so that the testosterone never has a surge at the beginning so that testosterone becomes lower much faster and stays lower during the course of treatment — what we call the sustained castration rate in these particular trials,” he said. “But, also interestingly, after you stop, it wears off more quickly and then the testosterone recovers more quickly.”
For example, researchers noted, in the Orgovyx and Firmagon patient arms 52% of patients (34 patients) and 16% (six patients) had testosterone levels return to baseline within 12 weeks of discontinuing treatment.
Furthermore, researchers stated that a previous study showed that among patients receiving long-term androgen deprivation therapy with an injectable drug at a median duration of 24 months, 47% of patients did not recover to normal testosterone levels within two years after stopping.“In contrast,” they wrote, “even after 48 weeks of [Orgovyx] treatment, most men recovered to normal testosterone levels within 90 days after discontinuing ADT.”
Side effects associated with lowered testosterone, Choudhury said, can include lowered sexual interest and sexual function as well as fatigue, hot flashes, moodiness, achiness and more concerning symptoms such as weight gain, increased blood sugar and cholesterol, and decreased muscle mass and bone mass.
“That’s why it’s very important that, after the treatment is done, that we want the testosterone to recover back to the normal range, so people are not having to deal with those sorts of long-term side effects,” he said.
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