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New data from a post hoc subgroup analysis from the Phase 3 TROPiCS-02 study evaluating sacituzumab govitecan-hziy* (Trodelvy®, Gilead Sciences) versus comparator chemotherapies (physicians’ choice of chemotherapy, TPC) in patients with HR+/HER2- metastatic breast cancer who progressed on endocrine-based therapies and at least two chemotherapies, showed an improved median progression-free survival (PFS) for sacituzumab govitecan, regardless of HER2 status.

The analysis examined progression-free survival (PFS) in the intention-to-treat population by HER2-immunohistochemistry (IHC) status, and the results demonstrated that sacituzumab govitecan improved median PFS vs. TPC in both HER2-low (IHC1+ and IHC2+/ISH-negative) and IHC0 groups.

The results of the analysis will be presented in a mini-oral session at 2022 annual meeting of the European Society for Medical Oncology (ESMO) 2022, held in Paris in the Évry Auditorium, Paris Expo Porte de Versailles, on September 10 (Abstract #1362, presentation #214MO). In addition, overall survival results will be included in a later-breaking oral session (#LBA76).

The study results confirmed that PFS efficacy with sacituzumab govitecan was consistent with observations in the TROPiCS-02 Intention-to-Treat Population.

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Summary of results
SC arm
TPC arm
SC arm
TPC arm
SC arm
TPC arm
Median PFS
Hazard ratio
(95% confidence
(0.53 – 0.83)


HR+/HER2- Breast Cancer
Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is the most common type of breast cancer and accounts for approximately 70% of all new cases, or nearly 400,000 diagnoses worldwide each year.

Almost one in three cases of early-stage breast cancer eventually become metastatic, and among patients with HR+/HER2- metastatic disease, the five-year relative survival rate is 30%. As patients with HR+/HER2- metastatic breast cancer become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy. In this setting, it is common to receive multiple lines of chemotherapy regimens over the course of treatment. However, the prognosis remains poor.

Sacituzumab govitecan is a first-in-class Trop-2 directed antibody-drug conjugate (ADC). Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Sacituzumab govitecan is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.

The drug is being evaluated in the TROPiCS-02 study, is a global, multicenter, open-label, Phase 3 clinical trial, randomized 1:1 to evaluate sacituzumab govitecan versus physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy for metastatic disease.

The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) for participants treated with Trodelvy compared to those treated with chemotherapy. Secondary endpoints include overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures.

Pre-treated metastatic cancer
“These data, to be presented at ESMO, demonstrate [the efficacy of sacituzumab govitecan] across HER2-low and IHC0 status in pre-treated metastatic breast cancer patients in the TROPiCS-02 trial,” explained Professor Peter Schmid, Professor of Cancer Medicine; Centre Lead, Centre of Experimental Cancer Medicine; Director, Barts Breast Cancer Centre.

“Once patients have developed resistance to endocrine-based therapies, their prognosis is extremely poor. The results highlight the potential for sacituzumab govitecan as a treatment option for people living with pre-treated HR+/HER2- metastatic breast cancer, regardless of their HER2-negative status,” Schmid added.

Strength of clinical activity
“These results show sacituzumab govitecan improved progression-free survival regardless of HER2 status in this pre-treated patient population and reinforce the strength of clinical activity in a population where need is highest,” noted Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology.

“Sacituzumab govitecan is already transforming the standard of care in second-line metastatic triple-negative breast cancer, and we’re excited about its potential in other breast cancers where there is significant need for new treatment options,” Grossman further noted.

In the study, HER2 negativity was defined per American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) criteria as immunohistochemistry (IHC) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH) test.

Sacituzumab govitecan has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication. Based on the data from the TROPiCS-02, Gilead has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA). The data will also shared with health authorities outside the U.S.

Clinical Practice Guidelines
Sacituzumab govitecan is currently included in the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®). The guidelines include a Category 1 recommendation for use in adult patients with second-line metastatic triple-negative breast cancer (defined as those who received at least two prior therapies, with at least one line for metastatic disease).

The guidelines also has a Category 2A preferred recommendation for investigational use in HR+/HER2- advanced breast cancer after prior treatment including endocrine therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy.

Sacituzumab govitecan has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.

Note: * sacituzumab govitecan-hziy is the register name in the United States only.  In the rest of the world this agency is referred to as sacituzumab govitecan.

Clinical trials
Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician’s Choice in Participants With HR+/HER2- Metastatic Breast Cancer (TROPiCS-02)

Highlights of prescription Information
Sacituzumab govitecan-hziy* (Trodelvy®, Gilead Sciences) [Prescribing Information]

[1] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer Version 4.2022. © National Comprehensive Cancer Network, Inc. 2022. Online. Last accessed Accessed on September 2, 2022.

Featured image: ESMO 2019 Congress being held in Barcelona, Spain, September 27 – October 1, 2019. Courtesy European Society for Medical Oncology (ESMO). Used with Permission.

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