TROPiCS-02: Efficacy of Sacituzumab Govitecan Within HER2-Negative Subsets of Breast Cancer

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In a post hoc analysis of the phase III TROPiCS-02 trial, sacituzumab govite­can-hziy improved efficacy outcomes in HER2-negative immunohistochemistry (IHC) subgroups.1 Results were consistent with those of the intent-to-treat population of hormone receptor–positive/HER2-negative advanced breast cancer, according to Frederik Marmé, MD, of Heidelberg University and University Hospital Mannheim in Germany, who presented these results at the European Society for Medical Oncology (ESMO) Congress 2022.

These data in HER2-low subgroups are generally consistent with the overall study results of the intent- to-treat population.
— Frederik Marmé, MD

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“Sacituzumab govitecan should be considered an effective treatment option for patients with hormone receptor–positive, HER2-negative metastatic breast cancer, regardless of HER2 IHC status,” Dr. Marmé said.

Sacituzumab govitecan, an antibody-drug conjugate that binds to trophoblast cell-surface antigen 2 (Trop2), is approved for patients with metastatic triple-negative breast cancer who have received at least two prior therapies, at least one for advanced disease. The phase III TROPiCS-02 trial found significant progression-free and overall survival benefits for this agent vs physician’s choice of chemotherapy in previously treated hormone receptor–positive, HER2-negative locally recurrent inoperable or metastatic breast cancer.2,3 At the ESMO Congress, Hope S. Rugo, MD, FASCO, reported median overall survival in this setting to be 14.4 months with sacituzumab govitecan vs 11.2 months with standard therapy (hazard ratio [HR] = 0.79; P = .020).3

Interest in targeting patients with “HER2-low” tumors has intensified since the DESTINY-Breast04 trial showed that a HER2-directed antibody-drug conjugate, fam-trastuzumab deruxtecan-nxki, resulted in significantly longer progression-free and overall survival than standard chemotherapy in metastatic HER2-low breast cancer.4

“HER2-low is a newly defined subcategory of HER2-negative breast cancer. It accounts for about 65% of all patients with hormone receptor–positive, HER2-negative breast cancer,” Dr. Marmé said. HER2-low tumors are defined as IHC 1+ or 2+ and in situ hybridization (ISH)-negative.

At the ESMO Congress, Dr. Marmé presented a post hoc analysis of the TROPiCS-02 HER2-negative population categorized as having HER2-low or HER2 IHC 0 advanced disease.


  • A post hoc analysis of the phase III TROPiCS-02 trial evaluated the efficacy of sacituzumab govitecan-hziy in HER2-negative IHC subgroups.
  • Improvement in progression-free survival was similar in the HER2-low and HER2 IHC0 subgroups, and similar to that seen in the full intent-to-treat population.
  • There is interest in evaluating treatments for the newly defined subset of HER2-low patients, within the HER2-negative subtype.

About TROPiCS-02  

TROPiCS-02 enrolled 543 patients whose disease progressed after at least two but no more than four lines of chemotherapy for metastatic disease. Prior treatment included at least one endocrine therapy, taxane, and inhibitors of cyclin-dependent kinases 4 and 6 in any setting. Patients were randomly assigned 1:1 to sacituzumab govitecan or treatment of physician’s choice (capecitabine, vinorelbine, gemcitabine, or eribulin).

For this subgroup analysis, local IHC and ISH results for the intent-to-treat population were analyzed retrospectively to determine the drug’s efficacy by HER2 IHC status. Within the population, 52% were HER2-low, 40% were HER2 IHC 0, and 8% were excluded from the analysis due to missing HER2 IHC status (essentially equal numbers of patients per arm). The primary endpoint was progression-free survival by blinded independent central review.

“Importantly, for this subgroup analysis, demographics and baseline characteristics were comparable between the two HER2-negative subgroups,” Dr. Marmé said. He further noted that characteristics were consistent with the overall population as well.

Improved Outcomes in Both HER2-Negative Subgroups

The latest analysis by IHC subgroup showed the median progression-free survival for sacituzumab govitecan vs standard therapy to be 6.4 vs 4.2 months, respectively, in the HER2-low group and 5.0 vs 3.4 months, respectively, in the IHC 0 group.

“Sacituzumab govitecan improved progression-free survival vs treatment of physician’s choice in both HER2-negative subgroups,” Dr. Marmé reported.

Median progression-free survival for the HER2-negative subgroups in the intent-to-treat population, for sacituzumab govitecan vs standard therapy, was reported as follows:

  • HER2-low subgroup (n = 283): 6.4 vs 4.2 months (HR = 0.58; P < .001)
  • HER2 IHC 0 subgroup (n = 217): 5.0 vs 3.4 months (HR = 0.72; P = .05)
  • IHC 1+ subset of HER2-low subgroup: 7.0 vs 4.3 months (HR = 0.57)
  • IHC 2+ subset of HER2-low subgroup: 5.6 vs 4.0 months (HR = 0.58)
  • TROPiCS-02 intent-to-treat population: 5.5 vs 4.0 months (HR = 0.66; P = .0003).

“These data in the HER2-low subgroups are generally consistent with the overall study results of the intent-to-treat population,” Dr. Marmé noted.

Overall response rate was highest among the HER2-low subgroup treated with sacituzumab govitecan—26% vs 12% with standard therapy (odds ratio [OR] = 2.52). For the HER2 IHC 0 subgroup, response in the sacituzumab govitecan arm was similar to controls—16% vs 15%, respectively (OR = 1.10). In the intent-to-treat population, the response rate was 21% with sacituzumab govitecan and 14% with standard therapy (OR = 1.63). The respective odds ratios for the drug’s impact on clinical benefit were 2.50, 1.61, and 1.84.

The safety profile of sacituzumab govitecan in the HER2-low and HER2 IHC 0 groups was generally consistent with that of the overall TROPiCS-02 safety population. 

DISCLOSURE: Dr. Marmé reported personal financial relationships with AstraZeneca, Clovis, GSK/Tesaro, Eli Lilly, Novartis, Pfizer, Roche, Myriad Genetics, PharmaMar, Eisai, MSD, Gilead, Pierre-Fabre, Agendia, Vaccibody, Genomic Health, Seagen, Pfizer, and Roche; and participation in data safety monitoring boards for Palleos and Amgen.


1. Schmid P, Cortes J, Marmé F, et al: Sacituzumab govitecan efficacy in HER+/HER2– metastatic breast cancer by HER2 immunohistochemistry status in the phase 3 TROPiCS-02 study. ESMO Congress 2022. Abstract 214MO. Presented September 10, 2022.

2. 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 40:3365-3376, 2022.

3. Rugo HS, Bardia A, Marmé F, et al: Overall survival results from the phase III TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in patients with HR+/HER2– metastatic breast cancer. ESMO Congress 2022. Abstract LBA76. Presented September 9, 2022.

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


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