Durvalumab With Olaparib and Paclitaxel for High-Risk HER2-Negative Stage II/III Breast Cancer: Results From the Adaptively Randomized I-SPY2 Platform Trial
41 Pages Posted: 19 Dec 2020 Publication Status: Review CompleteMore...
The combination of PD-L1-inhibitor durvalumab and PARP-inhibitor olaparib (DOP) in addition to standard neoadjuvant chemotherapy was investigated in the phase II I-SPY2 platform trial of stage II/III HER2-negative breast cancer. Seventy-three HER2-negative participants were randomized to DOP and 299 to standard of care control. DOP graduated in all subtypes, increasing pCR rates in all HER2-negative (22 to 37%), HR-positive/HER2-negative (14% to 28%), TNBC (27% to 47%). In HR-positive/HER2-negative cancers, pCR rate in MammaPrint ultra high (MP2) cases was considerably higher than MP1, 64% vs 22%. Overall,12.3% of patients in the experimental arm experienced immune-related grade 3 adverse events vs. 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has potential benefits over standard neoadjuvant therapy in HER2-negative early breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.
Keywords: Breast cancer; immunotherapy; DNA repair inhibitor; clinical trial
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