Updated HER2– Metastatic Breast Cancer Guideline Embraces Sacituzumab Govitecan

An updated guideline from the American Society of Clinical Oncology (ASCO) recommends that patients with hormone receptorpositive, HER2-negative metastatic breast cancer who are refractory to endocrine therapy would benefit from treatment with sacituzumab govitecan (Trodelvy).¹

The guideline, originally completed in 2021,² was updated to reflect findings from the phase 3 TROPiCS-02 trial (NCT03901339). The guideline update was well timed; a month after it was published, the FDA approved the use of sacituzumab govitecan for the treatment of adult patients with unresectable, locally advanced, or metastatic hormone receptor–positive, HER2-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+/in situ hybridization negative) breast cancer who have received endocrine-based therapy and at least 2 systemic regimens in the metastatic setting.³

The original guideline recommended that patients with hormone receptor–positive, HER2-negative metastatic breast cancer should be considered for single-agent chemotherapy, or a chemotherapy combination regimen in the case of highly symptomatic disease.

TROPiCS-02 was a global, randomized phase 3 study comparing the use of sacituzumab govitecan (n = 272), a Trop-2 antibody-drug conjugate, with physician’s choice of chemotherapy (n = 271) for patients with endocrine-resistant and unresectable, locally advanced, or metastatic hormone receptor–positive, HER2-negative breast cancer who were pretreated with chemotherapy. In the control arm, chemotherapy consisted of eribulin, capecitabine, gemcitabine, or vinorelbine.

At a median follow-up of 10.2 months, the median progression-free survival (PFS) by blinded independent central review was 5.5 months (95% CI, 4.2-7.0) and 4.0 months (95% CI, 3.1-4.4) with chemotherapy, meeting the primary end point of the trial (HR, 0.73; 95% CI, 0.60-0.88; P = .001).⁴

PFS rates were 46% with sacituzumab govitecan and 30% with chemotherapy at 6 months, and 21% vs 7%, respectively, at 12 months.

Objective responses were observed in 21% of patients in the sacituzumab govitecan arm and in 14% of the chemotherapy arm, with 2 patients in the investigational arm achieving a complete response. The median duration of response was 7.4 months (95% CI, 6.5-8.6) with sacituzumab govitecan and 5.6 months (95% CI, 3.8-7.9) with chemotherapy.

Overall survival (OS) results presented at the European Society for Medical Oncology Congress 2022 showed further benefit for the antibody-drug conjugate, with a median OS of 14.⁴ months with sacituzumab govitecan compared with 11.2 months with physician’s choice of chemotherapy (HR, 0.79; 95% CI, 0.65-0.96; P = .02).⁵

The agent was also considered to have a manageable safety profile. The most important and common treatment-related adverse events of grade 3 or higher with sacituzumab govitecan compared with chemotherapy were neutropenia (51% vs 38%) and diarrhea (9% vs 1%).

Following the release of the TROPiCS-02 data, the ASCO guideline’s expert panel, led by Beverly Moy, MD, MPH, clinical director of the Breast Oncology Program at Massachusetts General Hospital, conducted another search of literature to see whether any other randomized, controlled phase 3 trials could affect the patient population.

Looking at the study data, the panel recommended use of sacituzumab govitecan for this patient population.

References

1. Moy B, Rumble RB, Carey LA; Chemotherapy and Targeted Therapy for Endocrine-Pretreated or Hormone Receptor–Negative Metastatic Breast Cancer Expert Panel. Chemotherapy and targeted therapy for endocrine-pretreated or hormone receptor–negative metastatic breast cancer: ASCO guideline rapid recommendation update. J Clin Oncol. 2023;41(6):1318-1320. doi:10.1200/JCO.22.02807

2. Moy B, Rumble RB, Come SE, et al. Chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer that is either endocrine-pretreated or hormone receptor–negative: ASCO guideline update. J Clin Oncol. 2021;39(35):3938-3958. doi:10.1200/JCO.21.01374

3. U.S. FDA approves Trodelvy in pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead Sciences, Inc. February 3, 2023. Accessed February 16, 2023. https://bit.ly/3S9KbGK

4. Rugo HS, Bardia A, Marmé 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. doi:10.1200/JCO.22.01002

5. Rugo HS, Bardia A, Marmé F, et al. LBA76 Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). Ann Oncol. 2022;33(suppl 7):S1386. doi:10.1016/j.annonc.2022.08.012