SUBITO: Olaparib (PARP inhibitor) matches IACT (alkylator + auto-SCT) for 4-year OS in stage III HRD breast cancer

SUBITO (Phase 3, open-label; NCT02810743) randomized newly diagnosed stage IIIA–C, HER2-negative, HRD breast cancer (n=174; median age 42; 25%–32% gBRCA1/2+) to intensified alkylating chemotherapy with autologous stem cell rescue (ddAC → high-dose cyclophosphamide/thiotepa/carboplatin + auto-SCT) vs contemporary chemotherapy (ddAC → carboplatin/paclitaxel) followed by 1 year of olaparib 300mg BID. At median follow-up 41 months, 4-year OS was essentially identical: 77.0% with IACT vs 76.4% with chemo→olaparib (HR 1.11, 95% CI 0.57–2.17; p=0.37)—consistent with the modern PARP strategy established in high-risk gBRCA disease (eg, adjuvant olaparib improved 3-year iDFS to 85.9% vs 77.1% with placebo in OlympiA, albeit in a different population). Toxicity clearly favored the olaparib strategy: grade 3–4 thrombocytopenia 99% vs 19%, serious AEs 47% vs 26%, and febrile neutropenia 44% vs 12% (IACT vs olaparib arm); no treatment-related deaths were reported.