Trodelvy Now FDA Approved for HR-Positive, HER2-Negative Breast Cancer

JHOP - April 2023 Vol 13, No 2 - FDA Oncology Update

On February 3, 2023, the FDA approved a new indication for sacituzumab govitecan-hziy (Trodelvy; Gilead Sciences), a Trop-2–directed antibody–drug conjugate (ADC), in patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+/in situ hybridization–) breast cancer who have received endocrine-based therapy and ≥2 additional systemic therapies for metastatic disease. The FDA granted this application priority review.

The National Comprehensive Cancer Network now recommends sacituzumab govitecan as a category 1, preferred treatment for metastatic HR-positive, HER2-negative breast cancer, as defined in their Clinical Practice Guidelines in Oncology for breast cancer.

Sacituzumab govitecan was previously approved for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received platinum-containing chemotherapy and a PD-1 or a PD-L1 inhibitor and for the treatment of patients with unresectable or metastatic triple-negative breast cancer who previously received ≥2 systemic therapies (≥1 for metastatic disease).

This FDA approval was based on the results of the phase 3 TROPiCS-02 study (NCT03901339), a multicenter, open-label, randomized, clinical trial of 543 patients with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer that progressed after receiving, in any setting, a CDK4/6 inhibitor, endocrine therapy, and a taxane. Patients received ≥2 previous chemotherapies for metastatic disease (one of which could be neoadjuvant or adjuvant if the disease recurred within 12 months).

Patients were randomly assigned (1:1) to intravenous sacituzumab govitecan 10 mg/kg of body weight, on days 1 and 8 of a 21-day cycle, or to single-agent chemotherapy (chosen by the investigator before randomization from either eribulin, vinorelbine, gemcitabine, or capecitabine). Randomization was stratified by number of previous chemotherapy regimens for metastatic disease (2 vs 3 or 4), presence of visceral metastasis, and whether the patients received endocrine therapy in the metastatic setting for ≥6 months. Treatment continued until disease progression or unacceptable toxicity.

Progression-free survival (PFS) was the primary efficacy measure, and overall survival (OS) was among the secondary measures. The median PFS was 5.5 months (95% confidence interval [CI], 4.2-7.0) among patients who received sacituzumab govitecan and 4 months (95% CI, 3.1-4.4) among those who received single-agent chemotherapy (hazard ratio, 0.661; 95% CI, 0.529-0.826; P = .0003). In patients receiving sacituzumab govitecan, the median OS was 14.4 months (95% CI, 13.0-15.7), and it was 11.2 months (95% CI, 10.1-12.7) in patients receiving single-agent chemotherapy (hazard ratio, 0.789; 95% CI, 0.646-0.964; P = .02). This is the first OS benefit shown by a Trop-2–directed ADC in patients with HR-positive, HER2-negative metastatic breast cancer who received previous endocrine-based therapy and ≥2 chemotherapies.

The most common (≥25%) adverse events with sacituzumab govitecan in this study were decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, decreased lymphocyte count, diarrhea, fatigue, nausea, alopecia, increased glucose, constipation, and decreased albumin.

“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,” said principal trial investigator Hope S. Rugo, MD, Director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.

The recommended dose of sacituzumab govitecan-hziy is 10 mg/kg administered as an intravenous infusion once weekly on days 1 and 8 of 21-day treatment cycles until disease progression or unacceptable toxicity.

Related Items
FDA-Approved Nirogacestat Demonstrates Improved Patient Outcomes in Desmoid Tumor Management
Web Exclusives published on February 12, 2024 in FDA Oncology Update
Iwilfin FDA Approved for Adults and Pediatric Patients with High-Risk Neuroblastoma
Web Exclusives published on January 17, 2024 in FDA Oncology Update
Welireg Now FDA Approved for Patients with Advanced Renal Cell Carcinoma
Web Exclusives published on January 17, 2024 in FDA Oncology Update
Keytruda Plus Chemotherapy Receives New FDA Approvals for Advanced Biliary Tract Cancer and 2 Forms of Advanced Gastroesophageal Junction Adenocarcinoma
Web Exclusives published on December 19, 2023 in FDA Oncology Update
FDA Approved Loqtorzi, a PD-1 Inhibitor, for the Treatment of Adults With Metastatic or Recurrent Nasopharyngeal Carcinoma
Web Exclusives published on December 18, 2023 in FDA Oncology Update
Tibsovo FDA Approved for Patients With Relapsed Myelodysplastic Syndromes and IDH1 Mutation
Web Exclusives published on December 18, 2023 in FDA Oncology Update
Fruzaqla FDA Approved for Refractory Metastatic Colorectal Cancer
JHOP - December 2023 Vol 13, No 6 published on December 6, 2023 in FDA Oncology Update
Rozlytrek Now Approved for Pediatric Patients Older Than 1 Month With Solid Tumors and NTRK Gene Fusion and in New Oral Pellet Form
JHOP - December 2023 Vol 13, No 6 published on December 6, 2023 in FDA Oncology Update
FDA Authorizes Updated COVID-19 Vaccine Formulations for Better Protection Against Current Variants
JHOP - December 2023 Vol 13, No 6 published on November 17, 2023 in FDA Oncology Update
Bosulif Now FDA Approved for Pediatric Patients With Chronic Myelogenous Leukemia
JHOP - December 2023 Vol 13, No 6 published on November 3, 2023 in FDA Oncology Update
© Amplity Health. All rights reserved.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: