Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

Author(s): Hope S. Rugo, MD¹; Aditya Bardia, MD, MPH²; Frederik Marmé, MD, PhD³; Javier Cortes, MD, PhD^4,5; Peter Schmid, MD, PhD⁶; Delphine Loirat, MD, PhD⁷; Olivier Trédan, MD, PhD⁸; Eva Ciruelos, MD, PhD⁹; Florence Dalenc, MD, PhD¹⁰; Patricia Gómez Pardo, MD¹¹; Komal L. Jhaveri, MD¹²; Rosemary Delaney, MPH¹³; Olivia Fu, MD¹⁴; Lanjia Lin, PhD¹⁵; Wendy Verret, PhD¹³; and Sara M. Tolaney, MD, MPH¹⁶

Source: DOI: 10.1200/JCO.22.01002 Journal of Clinical Oncology 40, no. 29 (October 10, 2022) 3365-3376

Dr. Maen Hussein's Thoughts

Another option for HR+ /HER-2 negative pts who failed hormonal therapies, caution to toxicity though esp neutropenia and diarrhea, no OS data yet, will be interesting to know if it worth the adverse events at this stage of disease.

ABSTRACT

PURPOSE

Hormone receptor–positive (HR+) human epidermal growth factor receptor 2–negative (HER2–) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.

METHODS

In this global, randomized, phase III study, SG was compared with physician’s choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR+/HER2– locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival (PFS) by blinded independent central review.

RESULTS

Patients were randomly assigned to receive SG (n = 272) or chemotherapy (n = 271). The median age was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median PFS was 5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and 12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to 14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84; P = .14). Key grade ≥ 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%) and diarrhea (9% v 1%).

CONCLUSION

SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2– advanced breast cancer and limited treatment options.

Author Affiliations

¹Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; ²Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; ³Medical Faculty Mannheim, Heidelberg University, University Hospital Mannheim, Heidelberg, Germany; ⁴Medical Oncology Department, International Breast Cancer Center, Pangaea Oncology, Quironsalud Group, Madrid and Barcelona, Spain; ⁵Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain; ⁶Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; ⁷Medical Oncology Department and D3i, Institut Curie, Paris, France; ⁸Medical Oncology Department, Centre Léon Bérard, Lyon, France; ⁹Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain; ¹⁰Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France; ¹¹Hospital Universitari Vall D’Hebron, Barcelona, Spain; ¹²Memorial Sloan-Kettering Cancer Center, New York, NY; ¹³Department of Clinical Development, Gilead Sciences Inc, Foster City, CA; ¹⁴Department of Global Patient Safety, Gilead Sciences Inc, Foster City, CA; ¹⁵Department of Biostatistics, Gilead Sciences Inc, Foster City, CA; ¹⁶Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

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