Managing adverse events of sacituzumab govitecan

ABSTRACT

Introduction

The development of antibody-drug conjugates (ADCs) have revolutionized treatment for breast cancer. Sacituzumab govitecan (SG), a Trop2-targeted ADC, has demonstrated remarkable efficacy in triple-negative breast cancer (TNBC) and hormone receptor-positive metastatic breast cancer.

Areas covered

We summarize the evidence for SG use in the treatment of metastatic breast cancer, discuss the toxicity profile, and present strategies to manage adverse events.

Expert opinion

Hematologic toxicities are frequently observed with SG therapy. Neutropenia, reported in up to 72% of cases, often requires dose reductions or delays. Granulocyte colony-stimulating factor can be helpful in managing and preventing this toxicity. Anemia is another common toxicity and patients may require transfusions of packed red blood cells. Gastrointestinal toxicities are also common. A tailored regimen of prophylactic antiemetics (2–3 agents) should be initiated before SG infusion. For diarrhea, infectious workup should be considered on a case-by-case basis; patients should start loperamide and fluid/electrolyte replacement if necessary. Severe diarrhea associated with cholinergic syndrome should prompt the administration of atropine. Fatigue occurs in approximately half of the patients receiving SG, and <50% of patients experience complete alopecia during treatment. The approval of SG has significantly improved treatment outcomes; however, effective management of the toxicities is critical to optimize patient care and treatment adherence.

KEYWORDS:

• Antibody-drug conjugate
• gastrointestinal toxicities
• hematologic toxicities
• sacituzumab govitecan
• treatment outcomes
• UGT1A1 polymorphisms

Article highlights

• Sacituzumab govitecan (SG) is a novel antibody-drug conjugate (ADC) approved for the treatment of metastatic triple-negative breast cancer (TNBC) and hormone receptor-positive, HER2-negative breast cancer.

• Hematologic toxicities, such as neutropenia and anemia, are common with SG therapy and can be managed with granulocyte colony-stimulating factor (G-CSF) prophylaxis and supportive measures like packed red blood cell transfusions.

• Gastrointestinal toxicities, including nausea, vomiting, and diarrhea, are frequently observed with SG and can be effectively addressed with prophylactic antiemetics and appropriate symptomatic treatment.

• UGT1A1 polymorphisms, which affect the metabolism of SG’s cytotoxic payload, have been associated with increased toxicity of irinotecan, but routine testing is not recommended due to inconsistent data on cost-effectiveness.

• The approval of SG has significantly improved treatment outcomes for patients with TNBC and hormone receptor-positive, HER2-negative breast cancer, but comprehensive management strategies are necessary to optimize patient care and enhance treatment adherence.

• Ongoing research will further refine our understanding of these toxicities and guide the development of tailored strategies for optimal patient outcomes.

Declaration of interests

P Tarantino: Consulting fees: AstraZeneca, Daiichi Sankyo, Gilead, Genentech, Eli Lilly.

SM Tolaney: Consulting or advisory role for: Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Artios Pharma, Menarini/Stemline, Aadi Biopharma, Bayer, Incyte Corp., and Jazz Pharmaceuticals; and institutional research support from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, NanoString Technologies, Seattle Genetics, and OncoPep.

Reviewer disclosures

A peer reviewer on this manuscript has disclosed that they have received an honorarium from Gilead for giving an educational talk. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Kate Bifolck provided editorial support; she is a full-time employee of Dana-Farber Cancer Institute.

Additional information

Funding

This paper was not funded.