Fig. 2: Introducing a 48 h gap between carboplatin and olaparib treatments ameliorates the combination bone marrow toxicity effect while maintaining combination anti-tumour efficacy.

A Flow cytometry quantification of CD90+/Lineage− multipotent progenitor stem cells indicates that a 24 h gap between the carboplatin and olaparib combination is not sufficient to reduce bone marrow toxicity compared to concurrent treatment. Introduction of a 48, 72 or 96 h gap does reduce the combination toxicity effect to that seen for carboplatin alone. ANOVA statistical analysis of CD90+ cell levels from 6 biological replicates used a two-sided Student’s t test. P-values for the statistical significance of comparisons between the % CD90+/Lineage− multipotent progenitor stem cells treated with carboplatin alone and those involving concurrent or gap scheduling combinations with olaparib are indicated. B The use of a 48 h gap schedule for the carboplatin/olaparib combination still maintains greater anti-tumour efficacy in the TNBC gBRCAm PDX model HBCx-17 than the effects of either olaparib or carboplatin alone. Treatment represented by the black line is 28 d of vehicle control, the green line is 28 days (28D) daily 100 mg/kg olaparib starting on Day 1 (D1), the yellow line is a single D1 dose of 50 mg/kg carboplatin and the red line the single D1 50 mg/kg carboplatin and 28D daily 100 mg/kg olaparib treatment starting on D3. Mean tumour volumes are plotted along with error bars shown with ±SEM. Statistical significance was evaluated using a one-tailed t-test from 10 independent biological replicates for the vehicle control and 9 biological replicates for the other three treatment arms. Source data is provided as a Source Data file.