Introduction:

Olaparib is one of the first targeted therapies for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Data from the PROfound clinical trial showed that pts with homologous recombination repair gene mutations (HRRm) who received olaparib monotherapy had a longer treatment duration and improved progression-free survival (PFS) compared to pts who received physician’s choice of either enzalutamide or abiraterone. This study describes the timing and type of biomarker testing relative to olaparib monotherapy use and the real-world time on treatment (rwToT), real-world PFS (rwPFS), and real-world overall survival (rwOS) in pts with HRRm mCRPC treated with olaparib monotherapy.

Methods:

This retrospective study used data abstracted from electronic medical records in the ConcertAI Oncology Dataset. Pts with confirmed mCRPC, diagnosed between 2012 and 2023, age ≥21 years, treated with olaparib monotherapy (post-May 19, 2020) after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. HRR genes of interest were ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L. The timing of biomarker testing was evaluated from date of first documented biomarker test to start date of earliest olaparib monotherapy (index date). Somatic and germline testing was reported. Kaplan-Meier analysis was used to estimate median rwToT, rwPFS, and rwOS from the index date. Pts were stratified by line of earliest olaparib monotherapy and receipt of NHA with and without chemotherapy prior to initiation of olaparib monotherapy. Lines of therapy were evaluated from initial PC diagnosis.

Results:

A total of 144 pts with HRRm mCRPC treated with olaparib monotherapy were identified [median age 73 years; White 73.6%; ECOG PS 0-1 at index 78.4%; Gleason score ≥8 at index 66.7%; any BRCA mutation including co-occurring HRRm: 56.3%; median time from index: 8.1 months]. 41.0% initiated olaparib monotherapy in the first 3 lines (≤3L) and 59.0% fourth line and beyond (4L+). Overall, 54.9% of pts received chemotherapy before the index date.

The median time from first documented biomarker test date to index was longer in pts receiving olaparib in 4L+ and those who received chemotherapy pre-index date. Patients receiving olaparib in 4L+ had a higher numerical frequency of somatic testing than pts receiving olaparib in ≤3L (Table 1).

The median rwToT, rwPFS, and rwOS was numerically longer for pts receiving olaparib in 2L and 3L than 4L+ and for pts who had not received prior chemotherapy (Table 2).

Conclusion:

This analysis highlights the real-world biomarker testing patterns and treatment-related outcomes associated with olaparib monotherapy in pts with HRRm+ mCRPC. Pts may benefit from improved outcomes with earlier biomarker testing and treatment with targeted therapy when appropriate. Retesting for previously unrecognized or acquired mutations should also be considered.

Funding: This study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and AstraZeneca UK Ltd, who are codeveloping olaparib.