Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer

Abstract

Objective: To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease. Data Sources: A literature search was conducted utilizing PubMed and MEDLINE databases, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and September 3, 2020. Keywords included sacituzumab govitecan (-hziy), IMMU-132, Trop-2 (trophoblast cell-surface antigen 2), and TACSTD2. Study Selection and Data Extraction: All English-language trials involving sacituzumab govitecan for mTNBC were included and discussed. Data Synthesis: Sacituzumab govitecan is an antibody-drug conjugate targeted for Trop-2 and conjugated to the topoisomerase-1 inhibitor SN-38. It was granted accelerated Food and Drug Administration approval based on a phase I/II single-arm, multicenter study (n = 108), which reported an overall response rate of 33.3% and median duration of response of 7.7 months (95% CI = 4.9-10.8 months). Common adverse reactions include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, abdominal pain, and respiratory infection. A confirmatory, randomized phase III clinical trial is ongoing (NCT02574455). Relevance to Patient Care and Clinical Practice: This review covers the efficacy, safety, and clinical use of sacituzumab govitecan, a third-line drug with activity in mTNBC. Conclusion: Sacituzumab govitecan is a novel targeted treatment with promising activity in mTNBC.

UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation

“…To date, evidence for these other anticancer drugs has not been sufficiently strong to warrant considerations for UGT1A1 prescribing actions. Of interest, sacituzumab govitecan-hziy was recently approved to treat metastatic triple-negative breast cancer patients who have received at least two prior therapies for metastatic disease [ 91 , 92 ]. Sacituzumab govitecan is a Trop-2 directed antibody conjugated with the topoisomerase inhibitor SN-38.…”

“…The FDA-approved drug label states that UGT1A1*28 homozygotes have an increased risk of neutropenia, but limited data have been published regarding the association between UGT1A1 and sacituzumab govitecan toxicity [ 93 ]. Further analysis of clinical trial data, including the ASCENT trial, may provide additional insights on whether UGT1A1 polymorphisms influence sacituzumab govitecan toxicity [ 91 , 94 , 95 ].…”

An anti‑TROP2 monoclonal antibody TrMab‑6 exerts antitumor activity in breast cancer mouse xenograft models

“…Among them, antibody-drug conjugates (ADCs) are the main modality of antibody drugs (22). Recently, the first anti-TROP2 ADC, sacituzumab govitecan, which is a humanized IgG 1 conjugated to irinotecan metabolite (SN-38), has been approved by the US Food and Drug Administration against metastatic triple-negative breast cancers (23). ADCs have also been developed against hormone receptor-positive breast cancers and HER2-negative metastatic breast cancers (23).…”

“…Recently, the first anti-TROP2 ADC, sacituzumab govitecan, which is a humanized IgG 1 conjugated to irinotecan metabolite (SN-38), has been approved by the US Food and Drug Administration against metastatic triple-negative breast cancers (23). ADCs have also been developed against hormone receptor-positive breast cancers and HER2-negative metastatic breast cancers (23). Preliminary findings have demonstrated that datopotamab deruxtecan (DS-1062) is active in patients with advanced or metastatic non-small cell lung cancer (24).…”

“…In phase I trials of datopotamab deruxtecan, this drug induced responses in almost 25% of the patients trialed and had manageable side effects (24). The combination of these ADCs with immune checkpoint inhibitors is also expected to be effective (5,22,23,25).…”