Trodelvy® (sacituzumab govitecan-hziy)

Incidence and Management of Rash

This document is provided in response to your request for information about Trodelvy® (sacituzumab govitecan-hziy [SG]) and the incidence and management of rash.

Gilead continually assesses safety data from all sources for unidentified drug reactions and updates the product label information accordingly to reflect the safety profile of SG. Because case reports of potential adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. For this reason, Gilead does not provide information from post-marketing spontaneous reports.

Information summarized in this document includes data for SG monotherapy (10 mg/kg IV on Days 1 and 8 of a 21-day treatment cycle) from phase 2 and 3 clinical studies that constitute the largest pooled safety population of SG.

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings for neutropenia and diarrhea are available at:
www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.

Relevant Product Labeling1

Dosage and Administration

Recommended dosage

Premedication

Prior to each dose of SG, premedication for prevention of infusion reactions and prevention of chemotherapy‑induced nausea and vomiting is recommended. Premedicate with antipyretics, histamine-1 and histamine-2 blockers prior to infusion, and corticosteroids may be used for patients who had prior infusion reactions. Premedicate with a two or three drug combination regimen (eg, dexamethasone with either a 5‑hydroxytryptamine 3 receptor antagonist or a neurokinin‑1 receptor antagonist, as well as other drugs as indicated).

Dose modifications for adverse reactions

Infusion‑related reactions (IRRs)

Slow or interrupt the infusion rate of SG if the patient develops an IRR. Permanently discontinue SG for life-threatening IRRs.

Dose modifications for adverse reactions

Withhold or discontinue SG to manage adverse reactions as described in Table 1. Do not re‑escalate the SG dose after a dose reduction for adverse reactions has been made.

Table 1. Dose Modifications for Adverse Reactions1

Warnings and Precautions

Hypersensitivity and infusion-related reactions

Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with SG treatment. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions.

Incidence and Management of Rash in SG Clinical Studies

Pooled Safety Analysis

A pooled safety analysis (Figure 1) examined exposure to SG 10 mg/kg IV as monotherapy in 1063 patients from four studies of multiple epithelial tumors (IMMU-132-01,2 ASCENT,3 TROPiCS-02,4 and TROPHY-U-015-7). These studies included patients with metastatic triple negative breast cancer (mTNBC), hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2- mBC), and metastatic urothelial cancer (mUC).8

The median treatment duration of SG in this population was 4.1 (range: 0–‍63) mo1; rash was not among the most common (≥15%) treatment-emergent adverse events (TEAEs) reported.8

Figure 1. Pooled Clinical Studies8

Abbreviations: CKD4/6i, cyclin-dependent 4/6 inhibitor; CPI, checkpoint inhibitor therapies; PLT=platinum; TNBC, triple-negative breast cancer.

Premedication and Management of SG-Related Toxicities

Premedication for the prevention of IRRs such as rash included antihistamines that were to be administered before each SG infusion. Corticosteroids (hydrocortisone 50 mg or equivalent [oral or IV]) could also be administered prior to subsequent infusions if the patient experienced an IRR with a previous infusion.2,9-11

SG-associated toxicities were assessed and managed in accordance with standard clinical/institutional practices and accepted treatment guidelines.2,9-11

Metastatic Breast Cancer Studies

Treatment durations and rash-related safety data for the ASCENT study in patients with mTNBC are shown in Table 2. No frequency data are available for pre-infusion medication use of corticosteroids or systemic antihistamines for the prevention of IRRs in either treatment group.3 

Table 1. ASCENT: Treatment Duration and Rash-Related Safety Data in OSP3,12

Abbreviations: OSP=overall safety population; TPC=treatment of physicians’ choice; TRAE=treatment-related adverse event.

aTreatment durations for TPC agents: eribulin, 1.6 (0.03–15.3) mo; vinorelbine, 1 (0.03–11.5) mo; gemcitabine, 1.4 (0.2–8.1) mo; and capecitabine, 1.2 (0.3–10.6) mo. Data were unavailable for 6 patients who received capecitabine.

Within the TROPiCS-02 study in patients with HR+/HER2- mBC, IRRs were defined as symptoms, including rash, that occurred within the first 6 hours after SG administration and could occur at any cycle.10 Treatment durations and pre-infusion use of medications are shown in Table 2. Rash was not among the any-grade TRAEs with a reported incidence of ≥10%.13  

Table 2. TROPiCS-02: Treatment Duration and Pre-Infusion Medications4,14-16

aTreatment durations for TPC agents:  eribulin, 3.4 (0.03–18.3) mo; vinorelbine, 1.2 (0.03–8.1) mo; gemcitabine, 1.5 (0.03–22.3) mo; and capecitabine, 4.5 (0.2–12.9) mo.

bData are from the ITT population (N=543). Use of pre-infusion medication in the OSP was not reported.13

Metastatic Urothelial Cancer Study

Within the multi-cohort TROPHY-U-01 study in mUC, patients in Cohort 1 received a median of 6 SG cycles; treatment duration and rash-related TRAEs are shown in Table 3.17,18 All adverse events associated with rash were Grade ≤2.5

Table 3. TROPHY-U-01 Cohort 1: Treatment Duration and Rash‑Related TRAEs5,17

In Cohort 2, patients treated with SG had median (range) follow-up duration of 9.3 (0.5–‍30.6) mo; median treatment duration was not provided for this cohort. Rash was not among the reports of any-grade TRAEs with an incidence of >20%.18

IRRs were defined as symptoms, including rash, that occurred within the first 6 hours after SG administration and could occur at any cycle.11 No frequency data are available for pre‑infusion medication use for the prevention of IRRs in the SG arms within these two cohorts.5,17,18

Metastatic Epithelial Cancer Study

Within IMMU-132-01, in patients with various advanced epithelial cancers (including mTNBC, HR+/HER2- mBC, or mUC), 402 of the 495 patients in the OSP received SG 10 mg/kg.2 Treatment duration, rash-related safety data, and pre-infusion medications are shown in Table 4.

Table 4. IMMU-132-01 (OSP): Treatment Duration, Treatment-Related Rash, and Pre‑Infusion Medications2,19

References

1. TRODELVY® Gilead Sciences Inc. Trodelvy (sacituzumab govitecan-hziy) for injection, for intravenous use. U.S. Prescribing Information. Foster City, CA.
2. Bardia A, Messersmith WA, Kio EA, et al. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Ann Oncol. 2021;32(6):746-756.
3. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021;384(16):1529-1541.
4. Rugo HS, Bardia A, Marme F, et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022;40(29):3365-3376.
5. Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. J Clin Oncol. 2021;39(22):2474-2485.
6. Petrylak DP, Tagawa ST, Jain RK, et al. Early Results of TROPHY-U-01 Cohort 2: Sacituzumab Govitecan in Platinum-Ineligible Patients With Metastatic Urothelial Cancer Who Progressed After Prior Checkpoint Inhibitor Therapy [Poster]. Paper presented at: 2020 American Society of Clinical Oncology (ASCO) Meeting; 29 May - 2 June, 2020; Chicago, IL.
7. Loriot Y, Petrylak DP, Kalebasty AR, et al. TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes. Ann Oncol. 2024.
8. Rugo HS, Tolaney SM, Bardia A, et al. Pooled safety analysis of sacituzumab govitecan (SG) in multiple solid tumor types [Poster]. Paper presented at: American Society of Clinical Oncology (ASCO); May 31 - June 4, 2024; Chicago, IL.
9. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer [Protocol]. N Engl J Med. 2021;384(16):1529-1541.
10. Rugo HS, Bardia A, Marme F, et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer [Protocol]. J Clin Oncol. 2022;40(29):3365-3376.
11. 11. Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: A phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors [Protocol]. J Clin Oncol. 2021;39(22):2474-2485.
12. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer [Supplementary Appendix]. N Engl J Med. 2021;384(16):1529-1541.
13. Rugo HS, Bardia A, Marme F, et al. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer [Supplementary Appendix] J Clin Oncol. 2022;40(29):3365-3376.
14. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. The Lancet. 2023;402(10411):1423-1433.
15. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial [Supplementary Appendix]. The Lancet. 2023;402(10411):1423-1433.
16. Rugo HS, Bardia A, Marme F, et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer [Supplementary Appendix]. J Clin Oncol. 2022;40(29):3365-3376.
17. Tagawa ST, Balar AV, Petrylak DP, et al. Updated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan in patients with metastatic urothelial cancer who progressed after platinum-based chemotherapy and a checkpoint inhibitor [Poster 526]. Paper presented at: American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; 16-18 February, 2023; San Francisco, CA.
18. Petrylak DP, Tagawa ST, Jain RK, et al. Primary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan in platinum-ineligible patients with metastatic urothelial cancer who progressed after prior checkpoint inhibitor therapy [Presentation]. Paper presented at: American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; 16-18 February, 2023; San Francisco, CA.
19. Bardia A, Messersmith WA, Kio EA, et al. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial [Supplementary Appendix]. Ann Oncol. 2021;32(6):746-756.

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Trodelvy US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.

Follow-Up

For any additional questions, please contact Trodelvy Medical Information at:

☎1‐888-983-4668 or   www.askgileadmedical.com

Adverse Event Reporting

Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

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