A report on safety data from the phase 3 ASCENT trial evaluating sacituzumab govitecan (SG) in the treatment of metastatic triple-negative breast cancer (mTNBC) suggests this agent has a manageable safety profile in this population, including in patients aged 65 years and older.

However, there appears to be some variation in safety related to UGT1A1 genetic polymorphisms. The report was published in npj Breast Cancer.

The phase 3 ASCENT trial (ClinicalTrials.gov Identifier: NCT02574455) included patients who had relapsed or refractory mTNBC. Patients were randomly assigned to receive either SG or a single agent of the physician’s choice (TPC arm), which could involve eribulin, vinorelbine, gemcitabine, or capecitabine.


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Efficacy results were previously reported, showing favorable outcomes for the SG arm. In the current report, the researchers focused on safety, looking particularly at patient age and UGT1A1 variant status.

The safety population consisted of 258 patients in the SG arm and 224 patients in the TPC arm. The median patient age was 54 years in each arm. By the data cutoff of March 11, 2020, 17 patients were still receiving treatment in the SG arm, whereas 0 patients remained on treatment in the TPC arm. Most patients in either arm who discontinued treatment did so because of disease progression.

In the SG arm, the most common all-grade treatment-related adverse events (TRAEs) were neutropenia (63%), diarrhea (59%), and nausea (57%). The most common grade 3 or higher TRAEs were neutropenia (51%), leukopenia (10%), and diarrhea (10%).

The most common all-grade TRAEs in the TPC arm were neutropenia (43%), fatigue (30%), and nausea (26%). The most common grade 3 or higher TRAEs were neutropenia (33%), leukopenia (5%), anemia (5%), and fatigue (5%).

The safety profiles for patients aged 65 and older or 75 and older were reportedly similar to those for younger patients. In the SG arm, patients who were 65 and older more often had TRAEs leading to dose reduction than did younger patients, but this also occurred in the TPC arm.

UGT1A1 variant status was available for 250 patients in the SG arm. Variant status was wild type (*1/*1) in 44% of these patients; 37% had a *1/*28 genotype, and 13% had a *28/*28 genotype.

In the SG arm, among patients with a *28/*28 genotype, grade 3 or higher treatment-related neutropenia, febrile neutropenia, anemia, and diarrhea occurred at higher rates than those seen with *1/*28 and *1/*1 genotypes. The difference appeared greatest for treatment-related grade 3 or higher febrile neutropenia, which was reported in 18% of patients with a *28/*28 genotype, 5% of those with a *1/*28 genotype, and 3% of those with a *1/*1 genotype.

The researchers concluded that SG had a manageable safety profile, but patients with *28/*28 genotype for UGT1A1 should be more intensively monitored for adverse effects.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Rugo HS, Tolaney SM, Loirat D, et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer. 2022;8(1):98. doi:10.1038/s41523-022-00467-1

This article originally appeared on Oncology Nurse Advisor