HRD-targeted therapy offers less toxic alternative

The phase III SUBITO trial, led by researchers at the Netherlands Cancer Institute, prospectively evaluated whether IACT remains superior to a contemporary HRD-targeting strategy consisting of platinum-containing chemotherapy followed by one year of adjuvant olaparib. The results are now published in The Lancet Oncology.

A total of 174 patients with stage III HRD-positive breast cancer were randomized between the two treatment approaches. After a median follow-up of 41 months, four-year overall survival was virtually identical: 77.0% in the IACT arm and 76.4% in the chemotherapy-plus-olaparib arm. No subgroup derived a significant survival benefit from intensified chemotherapy.

Pathologic complete response rates were also comparable, occurring in approximately 40% of patients in both treatment groups. Patients who achieved a pathologic complete response had excellent outcomes, with four-year overall survival approaching 97% regardless of treatment assignment.

Importantly, intensified chemotherapy was associated with substantially higher toxicity. Serious adverse events occurred more frequently in the IACT arm, primarily driven by hematologic toxicity, including neutropenic fever.

The findings are particularly relevant given the historical debate surrounding high-dose chemotherapy in breast cancer. While earlier retrospective analyses suggested exceptional outcomes in HRD-positive tumors, SUBITO demonstrates that comparable survival can be achieved with a less toxic and more practical treatment strategy.

The investigators conclude that contemporary chemotherapy combined with adjuvant olaparib should be considered the preferred HRD-targeting approach for patients with stage III HER2-negative HRD-positive breast cancer.

Research at the NKI is financially supported by KWF Dutch Cancer Society and the AVL Foundation.