Olaparib + Durvalumab (PARP/PD-L1) Achieve 70% pCR, Early CD8+ Spike in TNBC

In the window-of-opportunity MEDIOLA Phase II trial (NCT03594396), 54 stage II/III triple-negative or ER-low breast-cancer patients received 4 weeks of olaparib (PARP inhibitor) with a single durvalumab dose before standard anthracycline/taxane neoadjuvant chemotherapy. Pathologic complete response reached 38/54 (70.4%), outstripping the ~33% pCR historically seen with chemotherapy alone and topping the 64.8% achieved with pembrolizumab-chemo in KEYNOTE-522. Homologous-recombination-deficient tumors (50%) showed higher early metabolic responses, and multiplex IHC revealed a two-week surge of exhausted (PD-1+/TIM3+) and activated (CD25+) CD8+ T-cells plus CD4+/CXCL13+ helpers that persisted through week 4, signalling rapid immune priming by PARP blockade. Baseline immune cell densities alone were not predictive.

https://aacrjournals.org/clincancerres/article/31/12_Supplement/PS12-01/753867/Abstract-PS12-01-Olaparib-induced-early-dynamics