On February 3, 2023, Gilead Sciences announced in a new press release that their targeted therapy Trodelvy received US Food and Drug Administration (FDA) approval for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer. To receive Trodelvy, patients must of had prior treatments with an endocrine therapy and two to four lines of chemotherapy for metastatic disease.

HR+/HER2- breast cancer is the most common type of breast cancer, with the National Cancer Institute (NCI) estimating 287,850 new cases of female breast cancer in 2022 alone.

“The FDA approval is an important step forward for both women and men living with metastatic breast cancer, especially for those individuals whose tumor is no longer responding to endocrine-based therapies and who are facing a poor prognosis,” said Laura Carfang, executive director, SurvivingBreastCancer.org, in the press release.

What does this Approval Mean for Breast Cancer Patients?

Current treatments for HR+ breast cancer patients include hormonal therapies, chemotherapies for those that do not respond to hormonal therapy alone and targeted therapies, either stand-alone or in combination with hormonal therapies.

“Despite decades of advances, people living with pre-treated HR+/HER2- metastatic breast cancer need new treatment options. Nearly all people with this type of breast cancer will eventually develop resistance to endocrine-based therapies and progress on available chemotherapies,” said Hope S. Rugo, MD, professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, US and principal investigator of the TROPiCS-02 study, in the press release.

“This approval is significant for the breast cancer community. We have had limited options to offer patients after endocrine-based therapy and chemotherapy, and to see a clinically meaningful survival benefit of more than three months with a quality of life benefit for these women is exceptional,” added Dr. Rugo.

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A total of 543 patients with HR+/HER2- metastatic breast cancer were enrolled into the TROPiCS-2 study (NCT03901339). This was a global, multicenter, open-label, Phase III study, randomized 1:1 to evaluate Trodelvy (sacituzumab govitecan-hziy) vs. the physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine or vinorelbine).

Patients had been treated with endocrine therapy, CDK4/6 inhibitor and previously failed at least two lines of chemotherapy. Participants received Trodelvy intravenously on Day 1 and Day 8 through a 21-day cycle.

The primary endpoint was progression-free survival (PFS) and secondary endpoints were objective response rate, overall survival, duration of response, clinical benefit rate, adverse events and abnormalities and quality of life .

A post-hoc data analysis revealed Trodelvy’s efficacy in pre-treated metastatic breast cancer patients that expressed low levels of HER2 and an IHC score of 0. Immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) scores determined HER2 expression levels as defined by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) criteria.

Trodelvy Improved Overall Survival by 3.2 months in HR+/HER2- Patients

The average five-year rate of survival is 30 percent in HR+/HER2- patients. In the TROPiCS-02 study, Trodelvy reduced disease progression or death by 34 percent. Compared with the physician’s choice of chemotherapy, Trodelvy demonstrated:

• A median overall survival of 14.4 months vs. 11.2 months on chemotherapy
• PFS of 5.5 months vs. 4 months on chemotherapy

In addition, 21 percent of patients of patients on Trodelvy were progression-free at one year vs. seven percent of those treated with chemotherapy. Trodelvy also improved the overall response rate of patients and the time to deteriorate quality of life measure.

Trodelvy is a Targeted Therapy

Trodelvy is a Trop-2 directed antibody-drug conjugate therapy. The Trop-2 protein marker is overexpressed in many types of cancers such as colorectal, ovarian, gastric and breast cancers. Since the upregulation of this marker was previously found necessary to drive tumor growth, it has been researched as a novel target for cancer therapies.

Trodelvy contains a monoclonal antibody linked to the anticancer cytotoxic drug SN-38. While the antibody recognizes and attaches to Trop-2, SN-38 blocks the enzyme topoisomerase I, preventing cancer cells from multiplying, leading to their eventual death.

What to Know Before Considering Trodelvy

Trodelvy is packaged in a single-use vial at a dosage of 180mg, to be delivered via an intravenous injection.

Warnings and precautions include neutropenia and diarrhea, hypersensitivity and infusion-related reactions, nausea and vomiting and embryo-fetal toxicity.

Some adverse reactions including laboratory abnormalities observed were decreased leukocyte count, decreased neutrophil count, decreased lymphocyte count, diarrhea, nausea, alopecia and fatigue.

Additional prescribing information can be found here.

Why Trodelvy Brings Hope

Currently, Trodelvy has been approved in more than 40 countries for treating metastatic triple-negative breast cancer patients — which accounts for about 10 to 15 percent of breast cancers — who have previously received two types of systemic treatments.

“We are pleased that Trodelvy could now provide new hope for people living with pre-treated HR+/HER2- metastatic breast cancer, building on the transformative role that Trodelvy is already playing for people with metastatic triple-negative breast cancer,” said Daniel O’Day, chairman and chief executive officer, Gilead Sciences.

In addition, this targeted therapy is also approved under accelerated approval for locally advanced or metastatic urothelial (bladder) cancer patients, who were previously given chemotherapy with a PD-1 or PDL-1 inhibitor.

“We need to combat this terrible disease, and all options that potentially slow its progress and extend life for those living with metastatic breast cancer are welcomed,” added Carfang in the same press release.