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5054 Background: Olaparib is one of the first targeted therapies for pts with mCRPC. Real-world data on treatment patterns prior to receiving olaparib are limited in mCRPC pts with homologous recombination repair gene mutation (HRRm). This study describes real-world novel hormonal agent (NHA) use by clinical setting prior to receiving olaparib in mCRPC and rwOS in pts with HRRm mCRPC treated with olaparib monotherapy. Methods: HRRm+ pts with confirmed mCRPC diagnosis, age ≥21 years, treated with olaparib monotherapy (post May 19, 2020) and prior to abiraterone or enzalutamide were abstracted from electronic medical records in the ConcertAI Oncology Dataset with PC diagnosis between 1990 and 2023. HRR genes of interest were ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L. Frequency of pts who progressed from metastatic hormone-sensitive PC (mHSPC) and from non-metastatic CRPC (nmCRPC) to mCRPC and treatment patterns prior to mCRPC were summarized. Kaplan-Meier analysis was used to describe the rwOS from the start date of earliest olaparib monotherapy treatment (index date). Results: A total of 144 mCRPC olaparib treated pts were identified median age 73 years; any BRCAm including co-occurring HRRm 56.3%; White 73.6%; ECOG 0-1 at index 78.4%; Gleason ≥8 at index 66.7%. Of the 144 pts, 80.5% of pts progressed from mHSPC, 11.8% of pts progressed from nmCRPC, and 7.6% of pts were identified in mCRPC setting. For pts who progressed from mHSPC, 62.1% were NHA-treated in the mHSPC setting. Overall, 43.8% initiated olaparib monotherapy in the first 2 lines of therapy after mCRPC diagnosis while 15.3% initiated olaparib in 5L+ (Table). Among pts diagnosed with mHSPC before mCRPC, olaparib was most frequently received in 2L (26.7%) and in 3L (22.4%). For mHSPC pts treated with NHA, olaparib was most frequently received in 2L (31.9%); in contrast, for mHSPC pts that were NHA-naïve, olaparib was most frequently received in the 5L+ (29.5%). The overall median rwOS from olaparib initiation was 16.5 (95% CI: 12.4, 21.1) months; and 20.3 (95% CI: 14.7, 26.8) and 12.9 (95% CI: 10.9, 16.9) months, respectively, for pts with and without any BRCA mutations. Conclusions: This real-world analysis indicates many mCRPC pts with HRRm are receiving several lines of therapy prior to olaparib, even when NHA are used prior to mCRPC. Earlier treatment with olaparib monotherapy may improve duration of therapy and overall survival. Table: see text
Kariburyo-Yay et al. (Sat,) studied this question.