TY - JOUR
T1 - Impact of Concomitant Prostate Cancer Medications on Efficacy and Safety of Relugolix Versus Leuprolide in Men With Advanced Prostate Cancer
AU - George, Daniel J.
AU - Saad, Fred
AU - Cookson, Michael S.
AU - Saltzstein, Daniel R.
AU - Tutrone, Ronald
AU - Bossi, Alberto
AU - Brown, Bruce
AU - Selby, Bryan
AU - Lu, Sophia
AU - Buckley, David
AU - Tombal, Bertrand
AU - Shore, Neal D.
N1 - Publisher Copyright:
© 2023
PY - 2023/6
Y1 - 2023/6
N2 - Background: To characterize the impact of concomitant prostate cancer treatments with the use of relugolix, the oral GnRH receptor antagonist, in advanced prostate cancer, a subgroup and pharmacokinetic/pharmacodynamic analyses of the HERO study was undertaken. Patients and Methods: Overall, 934 patients were randomized 2:1 to receive relugolix 120 mg orally once daily or leuprolide injections every 12 weeks for 48 weeks. In the setting of rising PSA, patients could receive enzalutamide or docetaxel 2 months after study initiation. Assessments included sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks and safety parameters. Subgroups analyzed included patients with or without concomitant enzalutamide or docetaxel. A sensitivity analysis of the primary endpoint was performed excluding patients who received concomitant therapies that may affect testosterone. Pharmacokinetic/pharmacodynamic analyses of 20 participants in the relugolix treatment group assessed the net effect of enzalutamide on exposure to relugolix. Results: Overall, 125 patients (13.4%) took concomitant therapies that could impact testosterone levels. Enzalutamide (n = 23) was the most frequently used therapy in the relugolix (2.7%) and leuprolide groups (1.9%). Docetaxel (n = 13) was used by 1.3% and 1.6% of patients in the relugolix and leuprolide groups, respectively. All other relevant concomitant therapy were used in <1% of population. Sensitivity analysis showed concomitant therapy did not impact the testosterone levels. Castration rates were similar with and without concomitant use of enzalutamide or docetaxel. No clinically relevant differences in adverse events were observed between subgroups in either treatment group. No differences in relugolix Ctrough or testosterone concentrations were observed, suggesting that any induction or inhibition properties of enzalutamide on relugolix metabolism result in a neutral net effect on relugolix exposure and testosterone suppression. Conclusion: Treatment with relugolix was associated with similar efficacy and safety profiles with and without concomitant enzalutamide or docetaxel. Standard-of-care use of relugolix in combination with these agents is supported by these data.
AB - Background: To characterize the impact of concomitant prostate cancer treatments with the use of relugolix, the oral GnRH receptor antagonist, in advanced prostate cancer, a subgroup and pharmacokinetic/pharmacodynamic analyses of the HERO study was undertaken. Patients and Methods: Overall, 934 patients were randomized 2:1 to receive relugolix 120 mg orally once daily or leuprolide injections every 12 weeks for 48 weeks. In the setting of rising PSA, patients could receive enzalutamide or docetaxel 2 months after study initiation. Assessments included sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks and safety parameters. Subgroups analyzed included patients with or without concomitant enzalutamide or docetaxel. A sensitivity analysis of the primary endpoint was performed excluding patients who received concomitant therapies that may affect testosterone. Pharmacokinetic/pharmacodynamic analyses of 20 participants in the relugolix treatment group assessed the net effect of enzalutamide on exposure to relugolix. Results: Overall, 125 patients (13.4%) took concomitant therapies that could impact testosterone levels. Enzalutamide (n = 23) was the most frequently used therapy in the relugolix (2.7%) and leuprolide groups (1.9%). Docetaxel (n = 13) was used by 1.3% and 1.6% of patients in the relugolix and leuprolide groups, respectively. All other relevant concomitant therapy were used in <1% of population. Sensitivity analysis showed concomitant therapy did not impact the testosterone levels. Castration rates were similar with and without concomitant use of enzalutamide or docetaxel. No clinically relevant differences in adverse events were observed between subgroups in either treatment group. No differences in relugolix Ctrough or testosterone concentrations were observed, suggesting that any induction or inhibition properties of enzalutamide on relugolix metabolism result in a neutral net effect on relugolix exposure and testosterone suppression. Conclusion: Treatment with relugolix was associated with similar efficacy and safety profiles with and without concomitant enzalutamide or docetaxel. Standard-of-care use of relugolix in combination with these agents is supported by these data.
KW - Androgen deprivation therapy
KW - Concomitant therapy
KW - Pharmacokinetic/pharmacodynamic analyses
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U2 - 10.1016/j.clgc.2023.03.009
DO - 10.1016/j.clgc.2023.03.009
M3 - Article
C2 - 37062659
AN - SCOPUS:85152694127
SN - 1558-7673
VL - 21
SP - 383-392.e2
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 3
ER -