Sequencing of therapeutic agents before and after metastatic castration-resistant prostate cancer (mCRPC) diagnosis in an international real-world setting.

100 Background: Over the last decade, many new approaches to mCRPC management have evolved. However, information is lacking on sequencing of active agents used pre- and post-mCRPC diagnosis in an international setting. In this real-world evidence study, we utilized an international registry of advanced prostate cancer patients to provide an overview of the use and sequencing of therapeutic agents. Methods: From an international (15 countries) advanced prostate cancer registry (IRONMAN, NCT03151629), we analyzed data from participants newly diagnosed with mCRPC between Jan 2018 and Dec 2021, who were followed through to Jul 2022. Eligible patients may have been diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) or m0CRPC before mCRPC. Demographic/clinical characteristics were reported, as well as pre-mCRPC diagnosis treatments, treatment after progression to mCRPC, and treatment sequence between last received pre-mCRPC and first-line (1L) treatment for mCRPC. Androgen deprivation therapy (ADT) was considered a backbone therapy in this analysis, meaning that we assumed patients likely received ADT along with the listed regimens; only ADT monotherapy is specifically called out. Results: 520 men were identified, predominantly from the USA (24%), Spain (20%), Canada (19%), and the UK (12%). At mCRPC diagnosis, median age was 72 years (interquartile range IQR 67–78), 73% of participants were White, and median PSA at mCRPC diagnosis was 9.15 ng/mL (IQR 2.57–41.49). Pre-mCRPC, the most common treatments were ADT monotherapy (57%) or in conjunction with chemotherapy (23%) or androgen receptor pathway inhibitors (ARPIs; 11%). Among participants receiving ARPIs pre-mCRPC (n=59), abiraterone (51%) and enzalutamide (47%) were most common. Post-mCRPC diagnosis, among all participants, ARPIs (79%) and chemotherapy (34%) were most prescribed through end of follow-up. Among those receiving ARPIs (n=413 participants), abiraterone (51%) and enzalutamide (55%) remained the most common (participants could have received >1 ARPI). The most frequent pre-mCRPC to 1L mCRPC sequence was ADT monotherapy to ARPI (37%) followed by chemotherapy to ARPI (15%). Of 190 participants receiving ADT monotherapy to ARPI, most were aged ≥75 years (54%), not metastatic at diagnosis (83%), and from Canada (29%), Spain (23%), or the USA (21%). Of 78 participants receiving chemotherapy to ARPI, many were aged 65–74 years (44%), diagnosed with de novo metastatic disease (54%), and from the UK (38%). Conclusions: Within the study period in the pre-mCRPC setting, ADT monotherapy was most frequently prescribed, and most patients did not receive ARPI. The most common mCRPC setting treatment was ARPI use. Management of patients pre- and post-mCRPC diagnosis may vary by country. In all, an unmet need exists for optimal therapy use at the earliest opportunity.