Prevention of sacituzumab govitecan-related neutropenia and diarrhea in patients with HER2-negative advanced breast cancer (PRIMED): an open-label, single-arm, phase 2 trial.

Background: Neutropenia and diarrhea are common sacituzumab govitecan-related adverse events, frequently leading to treatment modifications. PRIMED evaluated primary prophylactic granulocyte colony-stimulating factor (G-CSF) and loperamide to improve sacituzumab govitecan tolerability. Methods: PRIMED (NCT05520723) was an open-label, single-arm, phase II study that enrolled HER2-negative advanced breast cancer patients previously treated with 1-2 chemotherapy regimens for metastatic disease. Patients with hormone receptor positive tumors previously received CDK4/6 inhibitor in the advanced setting. Sacituzumab govitecan was administered until disease progression or unacceptable toxicity. G-CSF (5 MU/kg/day) and loperamide (2 mg/twice a day or 4 mg/day) were given during the first two cycles and at physician's discretion thereafter. Primary endpoints were (i) incidence of grade ≥3 neutropenia and (ii) incidence of grade ≥2 diarrhea, both assessed after two treatment cycles. Secondary endpoints included efficacy and extended safety. Findings: Between February 2023 and September 2023, 50 patients were enrolled. At data cut-off, median follow-up was 9.0 months (range, 0.2-13.5). Disease progression was the main reason for treatment discontinuation (33 patients, 66.0%). During the first two cycles, incidence of any grade neutropenia and diarrhea were 28.0% and 34.0%, respectively. Eight patients (16.0%) had ≥ grade 3 neutropenia, meeting this primary endpoint (p = 0.00023). No patients developed febrile neutropenia. Eight patients (16.0%) had ≥ grade 2 diarrhea (4.0% grade 3) (p = 0.084). The rate of adverse events associated with dose reductions and temporary treatment interruptions during the first two cycles was 14.0% and 30.0%, respectively. Interpretation: Primary prophylactic administration of G-CSF and loperamide resulted in a clinically relevant reduction of the incidence and severity of sacituzumab govitecan-related neutropenia and diarrhea. Funding: Gilead Sciences, S.L.U.