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 that this agent has a manageable safety profile in this population, including patients aged 65 years and older. However, there may be some variation in safety related to UGT1A1 genetic polymorphisms. The report was published in the journal npj Breast Cancer.

The pivotal, multicenter phase 3 ASCENT trial (ClinicalTrials.gov Identifier: NCT02574455) included patients who had relapsed or refractory mTNBC. Patients were randomly assigned to receive either SG (SG arm) or a single agent of the physician’s choice (TPC arm), which could involve eribulin, vinorelbine, gemcitabine, or capecitabine. Efficacy results had previously been reported for this trial, showing favorable outcomes for the SG arm. In this report, the researchers performing the analyses focused on safety, with some of the analyses focusing on patient age and UGT1A1 variant status.

The safety population was 258 patients in the SG arm and 224 patients in the TPC arm. Patient age was a median 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 remained on treatment in the TPC arm. Most patients in either arm who discontinued treatment did so because of disease progression.


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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 worse 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 worse TRAEs were neutropenia (33%) and leukopenia, anemia, and fatigue (5% for each).

The safety profiles for patients ages 65 and older or 75 and older were reportedly similar to those for younger patients, with similar rates of treatment-emergent adverse events. 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.

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

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

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

Disclosures: Some 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