Oncology Overview: Sacituzumab Govitecan-hziy (Trodelvy) for Triple-Negative Breast Cancer

Sacituzumab govitecan-hziy (Trodelvy) is a conjugated Trop-2-directed antibody and topoisomerase inhibitor for the treatment of patients with triple-negative breast cancer (mTNBC) who have received 2 prior therapies at minimum for metastatic disease.¹ The FDA approved sacituzumab govitecan-hziy April 7, 2021, under an accelerated approval based on duration and level of tumor response.¹

Indications and Dosages

Sacituzumab govitecan-hziy is indicated for adults.^1,2 It is not indicated for use with, or as a substitution for, other irinotecan-containing drugs due to a build-up of the active metabolite SN-38.²

Sacituzumab govitecan-hziy is dosed at 10 mg/kg (based on body weight at the beginning of each treatment cycle) on days 1 and 8 during continuous 21-day treatment cycles or until unacceptable toxicity.² It is a lyophilized powder that must be stored away from light in a refrigerator between 2° and 8°C.²

Before reconstituting, staff should warm the 180 mg vials to room temperature before adding 20 mL of 0.9% sodium chloride injection, USP.² The resulting mixture can take 15 minutes to fully dissolve, yielding a concentration of 10 mg/mL.²

The reconstituted solution is then added to a polypropylene bag of 0.9% sodium chloride injection, USP, to reach a concentration between 1.1 to 3.4 mg/mL. The total volume should not exceed 500 mL.²

For patients weighing more than 170 kg, the dose can be divided equally between two 500 mL bags.² Clinical staff must monitor patients during the infusion and for at least 30 minutes after an infusion has been completed. A dosing scheme, modified from package insert information, can be seen here:²

• Premedication
  • Infusion-related Reactions: antipyretics, H1 and H2 blockers, may consider corticosteroids if prior infusion reactions
  • Chemotherapy Induced Nausea and Vomiting: 2 or 3 drug combination (dexamethasone with a 5-HT3 or NK1 receptor antagonist, plus other indicated drugs)
• First Infusion: Administer dose over 3 hours, observe the patient for the entire infusion length and for 30 minutes after (total of 3.5 hours observation).
• Subsequent Infusion: Based on tolerability from first infusion, may infuse over 1 to 2 hours under observation and for 30 minutes after (total of 1.5 to 2.5 hours observation).

Mechanism of Action

Sacituzumab govitecan-hziy is an antibody drug conjugate composed of sacituzumab, a Trop-2-directed, fully humanized antibody, and SN-38, a topoisomerase 1 inhibitor.^1,2 Sacituzumab selectively binds Trop-2 and is internalized by the cancer cells.

Once internalized, SN-38 is released by hydrolysis where it interacts with topoisomerase 1.² The interaction prevents re-litigation of single-strand breaks caused by topoisomerase 1. The accumulation of single strand breaks leads to apoptosis.

Warnings and Adverse Events

Sacituzumab govitecan-hziy’s labeling carries boxed warnings for severe or life-threatening neutropenia and severe diarrhea.² It is contradicted in any patient who has had a severe hypersensitivity reaction to sacituzumab govitecan-hziy in the past.²

Clinicians should consider genetic typing before starting this medication for patients with reduced UGT1A1 activity, specifically homozygous for the UGT1A1*28 allele (incidence of grade 4 neutropenia 26% in homozygous patients vs 11% in patients homozygous for the wild type).²

At this time, it is not known whether clinicians should adjust doses for these patients, but they should monitor homozygous patients closely for severe neutropenia.² The table lists dose adjustments for severe neutropenia and other adverse reactions requiring dose adjustments:²