Do you recommend testing for UGT1A1 prior to initiating sacituzimab govitecan for patients with metastatic TNBC to mitigate neutropenia risk?

The phase I/II study of sacituzumab govitecan (SG) treated patients with various solid tumors and 146 patients had UGT1A1 testing.

Let's first look at diarrhea. The overall incidence of grade 3 diarrhea was low (6.8%) and could not be predicted by any of the three haplotypes at the 10 mg/kg dose level. Patients with *28*28 did have a higher incidence of grade 3 diarrhea at 16% but this group represented only 13% of the total population tested.

Thus, I would counsel that there is a small (5-8%) risk of diarrhea for the great majority of patients who receive SG and if one did have the *28*28 haplotype - a one out of eight chance - there is an 84% probability that the diarrhea will be grade 2 or less.

The same results were reported for neutropen...

I agree with Dr. @Dr. First Last's excellent response!

Having a UGT1A1 mutation or not wouldn't change my management.

Most cytotoxic chemotherapies cause diarrhea, and we manage it. The chemotherapy component of sacituzumab govitecan is SN38, a metabolite of irinotecan, which is so notorious for causing diarrhea that ALL patients are treated prophylactically and pro-actively. The incidence of diarrhea with sacituzumab govitecan is much lower than with irinotecan.

Neutropenia is common with or without a UGT1A1 mutation. In practice, I give peg-filgrastim 24-72 hours after the day 8 dose of sacituzumab govitecan to all of my patients. The patient has two weeks to recover her blood counts before the next dose.

I do not test for UGT1A1 mutation...