Introduction:

Leuprolide is an injected GnRH agonist that has been the standard of care for patients receiving androgen deprivation therapy (ADT) for advanced prostate cancer. In December of 2020, relugolix was approved as the first oral GnRH antagonist which provided patients with an alternative form of ADT. Results of the phase III HERO study associated relugolix use with faster recovery of testosterone and potentially fewer major adverse cardiovascular events (MACE). In this study, we sought to determine the clinical characteristics and cardiovascular outcomes of patients with prostate cancer treated with leuprolide or relugolix at our multi-centered academic institution.

Methods:

The Northwestern Electronic Data Warehouse was queried for men with an established diagnosis of prostate cancer for whom leuprolide was prescribed between January 2018-July 2022 or for whom relugolix was prescribed between December 2020-July 2022. Patients who were prescribed leuprolide were further stratified into a pre-relugolix era (January 2018-November 2020) and a post-relugolix era (December 2020-July 2022). Baseline clinicopathologic characteristics, Charlson Comorbidity Index (CCI), and cardiac outcomes following initiation of ADT were collected. MACEs were defined as non-fatal myocardial infarction (MI), non-fatal stroke, and death from any cause. Concurrent ADT use was defined as prescription of another form of ADT (darolutamide, enzalutamide, apalutamide, abiraterone, docetaxel, cabazitaxel) during the same period. Clinical variables were compared with one-way ANOVA, t-test, Chi square and Fisher’s exact test and statistical significance was defined as a p<0.05. Bonferroni correction was applied for the pairwise comparisons and statistical significance was defined as p<0.025.

Results:

403 men were prescribed leuprolide (n=225 in the pre-relugolix era, n=178 in the post-relugolix era) and 229 men were prescribed relugolix at our institution during the study period. Most patients (73%) had a history of at least one cardiovascular disease risk factor prior to initiation of therapy. Patients prescribed relugolix were overall younger, had fewer comorbidities, and were less likely to harbor metastatic disease (Tables 1,2). Following the initiation of ADT, 75 MACEs were observed. 44 occurred in the pre-relugolix leuprolide cohort, 15 occurred in the post-relugolix leuprolide cohort, and 16 occurred in the relugolix cohort. The respective incidences of major adverse cardiac events were 19.5%, 8.4%, and 7.0%. Death from any cause was the most common (n=52), followed by cerebral infarction (n=10), transient ischemic attacks (n=9), and acute MI (n=4). Of the deaths, 3, 0, and 3 were cardiac arrest or stroke for each cohort respectively.

Conclusion:

Our findings revealed similar incidences of MACEs for patients prescribed leuprolide or relugolix in the same period, however, patients who were prescribed leuprolide in the pre-relugolix era experienced a significantly greater incidence of MACEs. The higher rates observed in this cohort may be linked to the increased duration of follow-up and cumulative exposure to therapy. Due to the retrospective nature of the analysis, there were also significant limitations in regard to follow-up time and sample size for evaluation of MACEs. Ultimately, our results show a possible preference for initiation of relugolix in a younger population undergoing therapy for defined duration where rapid testosterone recovery may be favored.

Funding: N/A