Post-Conference Perspectives: ASCO GU 2021 - Episode 2

Advanced Prostate Cancer: New Findings From ASCO GU 2021

March 8, 2021
Neal Shore, MD, Carolina Urologic Research Center

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Dan George, MD, Duke Cancer Center

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Stephen Freedland, MD, Cedars-Sinai Medical Center

Dan George, MD, reviews new findings in advanced prostate cancer presented at ASCO GU 2021.

Dan George, MD: The report from ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium] 2021 on concomitant medication from the HERO study, men treated with relugolix or leuprolide for advanced prostate cancer was a pivotal trial to study the first oral GNRH antagonist relugolix, Orgovyx, in comparison with leuprolide. In this study, patients were randomized to 1 or the other 2:1 and treated for 48 weeks with continuous therapy. Patients were checked for testosterone suppression continuously, and overall relugolix demonstrated a 97% continuous suppression of testosterone throughout the study period, which was superior to that of leuprolide.

It also demonstrated a 54% reduction in the risk of cardiovascular events, in particular major adverse cardiovascular events, including stroke, heart attack, or sudden death. In recognizing this 48-week period, we anticipated that some patients would have some disease progression. In the HERO study, patients were allowed to have concomitant therapy for disease progression, because it has become common in patients with advanced prostate cancer with a disease progression, and treatments with novel androgen hormonal agents, such as enzalutamide or chemotherapy such as docetaxel.

In the study, roughly 2.7% of the patients on relugolix received concomitant enzalutamide, about 1.9% of those in the leuprolide arm received enzalutamide. Another 1.6% of patients with relugolix received docetaxel chemotherapy concomitantly and 1.9% of the leuprolide patients received docetaxel chemotherapy concomitantly. In addition, patients were allowed to receive radiation therapy, whether it be palliative or localized radiation therapy. In the relugolix arm, 15.5% of patients received concomitant radiotherapy and 18.8% of patients in the leuprolide arm received concomitant radiotherapy. When looking at these results, we recognize these numbers are relatively small for the systemic therapy arms, but with nearly 900 patients treated, there are enough data here for us to get an early look at the results of enzalutamide and docetaxel.

It appears throughout the population receiving those, both ruxolitinib and leuprolide testosterone levels remain suppressed. There is the pharmacodynamics effect with both agents and, in particular for relugolix, we saw over 95% continuous testosterone suppression throughout the study with receiving either enzalutamide and relugolix or docetaxel and relugolix. We also looked at the adverse-effect profiles for these concomitant therapies, including radiation therapy, and saw no new adverse-effect complications or signals. They were comparable in both arms, but there were higher rates of toxicity and grade 3 toxicity with both relugolix and leuprolide in combination with docetaxel or enzalutamide.

Relugolix is an effective agent as an androgen deprivation therapy for patients and can be combined with concomitant systemic therapies, including enzalutamide and docetaxel. Based on these data, a standard of care use of relugolix with radiotherapy is acceptable, given the continuous testosterone suppression effects, as well as the similar safety profiles. More studies will be needed to study combinations up front of relugolix with concomitant therapies to further define the efficacy and safety of these regimens.

It’s important to recognize that more commonly in our practice, antigen deprivation therapies are being combined with both local therapies and systemic therapies. And recognizing that even as patients progress from the castrate-sensitive to the castrate-resistant disease setting, ongoing antigen deprivation therapy is a de facto standard of care. It will be important to recognize that relugolix is highly effective in combination with systemic agents, including enzalutamide and docetaxel.

This can be effective in the castrate-resistant and castrate-sensitive prostate cancer settings. More studies and more data will be needed long term, and other agents will need to be looked at. But it’s promising to see that there doesn’t appear to be any drug interactions that would either elicit unexpected or more severe toxicities or that would affect pharmacodynamically the efficacy of relugolix in suppressing testosterone.

Transcript Edited for Clarity

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