Maarten van der Doelen

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

patients receiving at least one subsequent therapy after radium-223 was 84.6% in the DDR+ subgroup versus 73.8% in the DDR- subgroup; P = 0.409. A multivariate model included only DDR mutation status as prognostic factor of OS (Supplementary table 4). Nine patients (10%) with deleterious aberrations in BRCA1 or BRCA2 were identified. The median overall survival of these patients was significantly longer when compared to patients with wildtype BRCA (median 36.8 months vs. 20.5 months; HR 2.73; 95% CI 1.06-7.07; P = 0.038). For all secondary endpoints no differences were seen.

A

DDR + DDR -

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Results of the exploratory analysis between the HRD subgroups were in line with the differences between the DDR+ and DDR- subgroups (Supplementary table 5). 150

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A

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DDR + DDR -

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150 -50

100 -100

Maximal change from baseline (%)

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0

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Maximal change from baseline (%)

B

DDR + DDR -

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7

150

100

50

B

0

DDR + DDR -

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150 -50

100 -100

Maximal change from baseline (%)

50 Figure 3. Waterfall plots of best biochemical response during therapy, stratified by DNA damage response (DDR) mutation status. A. Prostate-specific antigen (PSA). B. Alkaline phosphatase (ALP).

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Maximal change from baseline (%)

185