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

Article

Sacituzumab govitecan-hziy (Trodelvy) is indicated for the treatment of patients with triple-negative breast cancer who have received 2 prior therapies at minimum for metastatic disease.

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

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