Real-world data presented at the 2024 Society of Urologic Oncology (SUO) Annual Meeting suggests that olaparib provides clinical benefit to patients with metastatic castration-resistant prostate cancer (mCRPC) who have homologous recombination repair (HRR) mutations. The study, led by Dr. Daniel George, analyzed real-world treatment patterns and clinical outcomes in these patients within the United States.
The study used data from the ConcertAI Oncology Dataset, a collection of de-identified electronic medical records from diverse practice locations across the US. Researchers identified 144 patients with confirmed mCRPC, diagnosed between 2012 and 2023, who received olaparib monotherapy after prior treatment with abiraterone or enzalutamide and had positive HRR mutation status. The HRR genes of interest included ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L.
Treatment Patterns and Outcomes
The analysis revealed that 41% of patients initiated olaparib monotherapy within the first three lines of therapy, while 59% received it in the fourth line or later. The median age of the patients was 73 years, with the majority being white (73.6%) and having an ECOG performance status of 0-1 (78.4%). A significant proportion (56.3%) had a BRCA mutation, including co-occurring HRR mutations. The median time from the start of olaparib treatment to the end of the record was 8.1 months for those receiving treatment in the first three lines and 7.7 months for those receiving it in later lines.
The median real-world time on treatment with olaparib monotherapy was 4.6 months (95% CI 3.5 - 5.5). For patients receiving olaparib in the first three lines, the median time on treatment was 5.3 months (95% CI 4.0 – 8.2), compared to 3.8 months (95% CI 2.1 – 5.5) for those receiving it in later lines.
The median real-world progression-free survival (rwPFS) for the entire cohort was 4.5 months (95% CI 3.6 - 5.6). Patients treated with olaparib in the first three lines had a median rwPFS of 5.3 months (95% CI 3.6 – 6.8), while those treated in later lines had a median rwPFS of 3.9 months (95% CI 3.2 – 5.5).
The median real-world overall survival (rwOS) for the entire cohort was 16.5 months (95% CI 12.4 - 21.2). The median rwOS was 16.5 months (95% CI 11.7 – 24.1) for patients treated with olaparib in the first three lines and 15.0 months (95% CI 11.0 – 21.0) for those treated in later lines.
Implications and Limitations
Dr. George emphasized that many patients received olaparib in later lines of therapy, potentially missing out on the full clinical benefit. Despite this, the real-world progression-free and overall survival results were similar to those observed in the PROfound clinical trial, which compared olaparib to enzalutamide or abiraterone in patients with HRR-mutated mCRPC. The PROfound trial demonstrated that olaparib monotherapy resulted in a longer treatment duration (median 7.6 vs. 3.9 months), improved progression-free survival (median 5.8 vs. 3.5 months), and improved overall survival (median 17.3 vs. 14.0 months) compared to physician's choice of enzalutamide or abiraterone.
The authors noted several limitations to the real-world study, including its retrospective design, the potential for unmeasured confounders due to small sample sizes, and the fact that most patients were treated in community oncology practices within the US. Additionally, outcomes were measured from the initiation of olaparib monotherapy, unlike the PROfound trial, which measured outcomes from the time of randomization. The retrospective nature of the study and reliance on electronic medical record data also introduced potential limitations related to data availability and provider documentation practices.
Conclusion
Despite these limitations, the study suggests that earlier biomarker testing could lead to earlier treatment with targeted therapy, potentially improving outcomes for patients with mCRPC. The findings underscore the importance of identifying HRR mutations early in the disease course to optimize treatment strategies and improve patient outcomes.
