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. 2025 Jun 18:85:103309.
doi: 10.1016/j.eclinm.2025.103309. eCollection 2025 Jul.

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

José Manuel Pérez-García  1   2   3 , María Gion  1   4   5   3 , Manuel Ruiz-Borrego  6 , Isabel Blancas  7   8   9 , Elena López-Miranda  1   4   3 , Salvador Blanch  10 , Sabela Recalde  11 , Cristina Reboredo Rendo  12 , Xavier González  13 , Nerea Ancizar  14 , Serafin Morales  15 , Patricia Cortez  5   16 , Zuzanna Piwowarska  1   3 , Eileen Shimizu  1   3 , José Antonio Guerrero  1   3 , Miguel Sampayo-Cordero  1   3 , Alejandro Martínez-Bueno  17 , Javier Cortés  1   2   5   18   19   3 , Antonio Llombart-Cussac  1   20   21   3
Affiliations

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

José Manuel Pérez-García et al. EClinicalMedicine. .

Abstract

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.

Keywords: Advanced breast cancer; Diarrhea; Hormone receptor-positive/HER2-negative; Neutropenia; Sacituzumab govitecan; Triple-negative.

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Conflict of interest statement

JMPG reports employee at MEDSIR; Advisory Role (Lilly, Roche, Eisai, Daichii Sankyo, AstraZeneca, Seattle Genetics, Gilead); Travel expenses (Roche). MG reports honoraria (Roche, Novartis, Gilead, Daiichi-Sankyo); Travel grants and Accommodation (Roche, Pfizer, Daiichi-Sankyo). MRB reports speaker grants (Novatis, Lilly, AstraZeneca, Daiichi, Gilead); Advisory board (AstraZeneca, Daiichi, Novartis); and Travel funding (Roche). IB reports grants and research support to the Institution (Agendia, AstraZeneca, Lilly, Pfizer and Roche); Honoraria and advisor colaboration (AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Eisai, Gilead, Grünenthal, GSK, Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Roche, Seagen and Veracyte); Support for attending meetings and/or travel (AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Lilly, Novartis, Pfizer, Pierre-Fabre and Roche). ELM reports honoraria and advisor collaboration (AstraZeneca, Daiichi Sankyo and Lilly); Support for attending meetings and/or travel (Gilead, AstraZeneca, Daiichi Sankyo, Novartis and Roche). SR reports support for attending meetings and/or travel (Daiichi Sankyo, Lilly, Novartis, and Roche). XG reports honoraria as an invited speaker (Novartis, Pierre Fabre, Gilead). ZP, ES, JAG and MSC report MEDSIR employment. AMB reports honoraria as an invited speaker (AstraZeneca, Roche, Seagen); Travel expenses, accomodation and registration fees (GSK, Roche, Seagen). JC reports Consulting/Advisor for Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharp&Dohme, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Scorpion Therapeutics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, Abbvie, BridgeBio, Biontech, Biocon, Circle Pharma, Delcath Systems, Inc., Hexagon Bio; honoraria from Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharp&Dohme, Daiichi Sankyo, Astrazeneca, Gilead, Steamline Therapeutics; research funding to the Institution from Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffman–La Roche, Guardanth health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Iqvia, Queen Mary University of London; stock for MAJ3 Capital, Leuko (relative); travel and accommodation expenses from Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, Astrazeneca, Gilead, Merck Sharp&Dhome, Steamline Therapeutics; patents (Pharmaceutical Combinations of A Pi3k Inhibitor And A Microtubule Destabilizing Agent. Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde. WO 2014/199294 A. ISSUED; Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Aleix Prat, Antonio Llombart, Javier Cortés.US 2019/0338368 A1. LICENSED). ALC reports Research support from Roche, Agendia, Lilly, Pfizer, Novartis, Merck Sharp&Dhome, Gilead, Daiichi Sankyo; consulting/advisor fees from Lilly, Roche, Pfizer, Novartis; speaker's bureaus for Lilly, Astrazeneca, Merck Sharp&Dhome, Pfizer, Novartis; travel support from Roche, Pfizer, Astrazeneca, Steamline therapeutics, Merck Sharp&Dhome; patents (Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Aleix Prat, Antonio Llombart, Javier Cortés.US 2019/0338368 A1. LICENSED); stock or other ownership in MAJ3 Capital & Initia-Research. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Trial profile.
See this image and copyright information in PMC

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