Maarten van der Doelen

Impact of DNA damage repair defects on response to radium-223 therapy in mCRPC patients

Between the DDR+ and DDR- subgroups, no statistically significant differences in baseline characteristics were found (Table 1). Median age was 68 years and 55.9% of the patients underwent prior taxane-based chemotherapy, either upfront in hormone sensitive (30.0%) or in the castration-resistant state (70.0%). Seventy-one percent of the patients had baseline Eastern Cooperative Oncology Group performance status 0. Twelve (12.9%) patients received a concomitant systemic agent during radium-223, of which nine (75.0%) received either abiraterone or enzalutamide, and three (25.0%) received concurrent Sipuleucel-T. The percentage of patients who received concomitant agents was equally distributed across the DDR+ and DDR- subgroup (10.7% vs. 13.8%) (Supplementary table 1). Outcomes The median OS of the total cohort was 21.0 months (95% CI 18.3-23.6). DDR+ patients had a statically significant longer median OS compared to DDR- patients (median 36.3 vs. 17.0 months; HR 2.29; 95% CI 1.21-4.32; P = 0.011) (Figure 2A). Secondary endpoints TAP and TST favoured the DDR+ group when compared with the DDR- group, although with borderline insignificance. Sixty-eight (73.1%) patients developed ALP progression before initiation of a subsequent systemic therapy. The median TAP was 6.9 months for DDR+ patients, compared to 5.8 months for DDR- patients (HR 1.48; 95% CI 0.87-2.50; P = 0.146) (Figure 2B). At time of evaluation, 71 (76.3%) patients had started a subsequent therapy after radium-223. The median TST in the DDR+ group was 8.9 months, compared to 7.3 months in the DDR- group; P = 0.083; HR 1.58; 95% CI 0.94-2.64) (Figure 2C). No statistically significant difference was found in the TSRE (Figure 2D).

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