202 Background: Both olaparib and lutetium-177-PSMA-617 have been approved for post-taxane and post-ARPI (androgen receptor pathway inhibitor) metastatic castration-resistant prostate cancer (mCRPC). However, optimal sequencing or superior selection between the two agents to maximize clinical outcomes and survival is unclear. Here, we compare the overall survival (OS) among patients who received either agent following prior systemic therapy, comparing regimens that included androgen receptor targeted therapy with or without chemotherapy. Methods: A retrospective analysis using the TriNetX database identified patients diagnosed with prostate cancer from 2000–2024. Patients were grouped by treatment with docetaxel (doc), enzalutamide (enz), or abiraterone (abi) alone or in combination, followed by either olaparib or lutetium-177-PSMA-617. Overall (OS) and 1-year survival were estimated via Kaplan-Meier analysis, with group differences assessed by log-rank test yielding hazard ratios (HR) and 95% confidence intervals. Incidence of anemia and neutropenia at 180 days was also compared. Results: A total of 1,832 patients who met the inclusion criteria were identified, and 1,238 after matching. Propensity matching was performed between groups that ultimately received either olaparib or lutetium-177-PSMA-617; of these, a combined 190 received doc+abi, 104 received doc+enz, 354 received doc+abi+enz, 212 received enz+abi, 212 received abi, and 166 received enz. There was a statistically significant difference in OS when comparing Olaparib vs lutetium-177-PSMA-617 after receiving doc+abi of 10.1 vs 15.9 months (HR = 1.43; 95% CI 0.98 - 2.10), as well as after enz (18.1 months vs time not reached for lutetium-177-PSMA-617, HR = 2.03; 95% CI 1.17 – 3.51). Comparisons done between post-taxane and post-ARPI groups also saw lower 1-year survival post-ARPI with olaparib vs lutetium-177-PSMA-617 of 60.6% vs 67.0% (HR = 1.34; 95% CI 1.01 – 1.79). Olaparib used was also associated with higher rates of anemia with doc+abi (HR = 1.47; 95% CI 1.05 - 2.06), doc+abi+enz (HR = 1.34; 95% CI 1.05 – 1.71), and enz (HR = 1.71; 95% CI 1.12 – 2.60). No significant differences were observed for neutropenia. Conclusions: This real-world study potentially suggests superior OS in men with metastatic prostate cancer receiving lutetium-177-PSMA-617 over Olaparib, particularly when given post-ARPI. Further prospective studies are needed to confirm these findings. Group Median OS (months) p HR (95% CI) doc + abi 10.1 vs 15.9 0.064 1.43 (0.98–2.10) doc + enz 14.2 vs 11.7 0.588 1.15 (0.69–1.93) doc+abi+enz 12.9 vs 15.4 0.168 1.20 (0.92–1.57) enz+abi 15.1 vs 17.6 0.124 1.36 (0.92–2.00) abi 18.8 vs NR 0.355 1.24 (0.78–1.97) enz 18.1 vs NR 0.01 2.03 (1.17–3.51) All groups compare Olaparib vs lutetium-177-PSMA-617 after the listed medications in any order.
Shirodkar et al. (Sun,) studied this question.