Extended Follow-up of TROPiCS-02 Trial: Sacituzumab Govitecan in Metastatic Breast Cancer

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Additional follow-up of the phase III TROPiCS-02 trial has upheld the progression-free and overall survival benefit seen with sacituzumab govitecan-hziy compared with physician’s choice of treatment in patients with endocrine-resistant, hormone receptor–positive, HER2-negative metastatic breast cancer.1 Sacituzumab govitecan reduced the risk of disease progression or death by 35% and the risk of death by 21%, according to Sara M. Tolaney, MD, MPH, Associate Professor of Medicine at Harvard Medical School and Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, who presented the findings at the 2023 ASCO Annual Meeting.

“In this exploratory analysis of the TROPiCS-02 phase III trial, extended follow-up of about 13 months demonstrated durable efficacy of sacituzumab govitecan vs treatment by physician’s choice, with continued improvements in progression-free and overall survival…. A higher proportion of patients remained alive, and progression-free, at each landmark,” Dr. Tolaney said. “The enduring benefit seen with additional follow-up reinforces sacituzumab govitecan as an important novel therapy for patients with pretreated, endocrine-resistant, hormone receptor–positive, HER2-negative metastatic breast cancer.”

Sara M. Tolaney, MD, MPH

Sara M. Tolaney, MD, MPH

Sacituzumab govitecan is a first-in-class antibody-drug conjugate targeting TROP-2, a transmembrane calcium signal transducer commonly expressed in multiple breast cancer subtypes. It is approved for the second line or later in metastatic triple-negative breast cancer in multiple countries and for hormone receptor–positive, HER2-negative metastatic breast cancer in the United States, based on earlier results of TROPiCS-02.2

About TROPiCS-02

The trial enrolled 543 patients with metastatic or locally recurrent and inoperable hormone receptor–positive, HER2-negative breast cancer that had progressed after at least one endocrine therapy, taxane, and CDK4/6 inhibitor and after at least two (but no more than four) lines of chemotherapy for metastatic disease. Patients were randomly assigned to receive physician’s choice of treatment (capecitabine, vinorelbine, gemcitabine, eribulin) or sacituzumab govitecan at 10 mg/kg on days 1 and 8 every 21 days.

The data cutoff for the current analysis was December 1, 2022, giving a median follow-up of 12.8 months. This exploratory analysis of overall survival was based on 438 events, which included 96 new deaths.

The key findings for sacituzumab govitecan vs standard therapy with additional follow-up are listed here:

  • Median progression-free survival: 5.5 months vs 4.0 months (hazard ratio [HR] = 0.65; P = .0001)
  • Progression-free survival at 18 months: 14.4 months vs 4.7 months
  • Median overall survival: 14.5 months vs 11.2 months (HR = 0.79; P = .0133)
  • Overall survival rate at 18 months: 39.2% vs 31.7%
  • Overall survival rate at 24 months: 25.7% vs 21.1%
  • Progression-free and overall survival benefits generally observed across predefined subgroups.

Results by TROP-2 Expression and HER2 Status

The improvements with sacituzumab govitecan were seen regardless of TROP-2 expression level and HER2 status, which is consistent with a previous analysis.3 The hazard ratios for progression-free survival were 0.79 for patients with a TROP-2 H-score up to 100 and 0.61 for those with an H-score of at least 100; for overall survival, the hazard ratios were 0.78 and 0.82, respectively. By HER2 expression, the hazard ratios for progression-free survival were 0.60 for HER2-low patients and 0.70 for HER2-negative patients, whereas those for overall survival were 0.75 and 0.85, respectively, Dr. Tolaney reported.

“Sacituzumab govitecan prolonged duration of response compared with treatment by physician’s choice, at longer follow-up, which is consistent with the previous analysis,” she added. Median duration of response was 8.1 months vs 5.6 months, respectively.

Safety Profile

“Overall, the safety profile in this analysis was consistent with that of previous studies. No new safety signals emerged with further follow-up,” stated Dr. Tolaney.

Grade ≥ 3 treatment-emergent adverse events were reported in 74% of patients treated with sacituzumab govitecan and 60% of patients treated with physician’s choice; they led to treatment delays in 66% and 44%, respectively, and treatment discontinuation in 6% and 4%, respectively. There were six fatal treatment-emergent adverse events with sacituzumab govitecan, one of which was considered related to treatment, and none in the control arm. 

DISCLOSURE: This research was supported by Gilead Sciences. Dr. Tolaney has had a consulting or advisory role with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, and Bayer; and has received research funding from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics.


1. Tolaney SM, Bardia A, Marmé F, et al: Final overall survival analysis from the phase 3 TROPiCS-02 study of sacituzumab govitecan in patients with hormone receptor–positive/HER2-negative metastatic breast cancer. 2023 ASCO Annual Meeting. Abstract 1003. Presented June 5, 2023.

2. Modi S, Jacot W, Yamashita T, et al: Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 387:9-20, 2022.

3. Schmid P, Cortés J, Marmé F, et al: Sacituzumab govitecan efficacy in hormone receptor–positive/HER2-negative metastatic breast cancer by HER2 immunohistochemistry status in the phase III TROPiCS-02 study. ESMO Congress 2022. Abstract 214MO. Presented September 10, 2022.


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