Sacituzumab Govitecan Shows Strong ORR, PFS Benefit in HER2-Low/IHC0 Metastatic Breast Cancer

The antibody-drug conjugate sacituzumab govitecan demonstrated superior overall response rate and progression-free survival in patients with breast cancer with limited options due to lack of high HER2 expression.

A subgroup analysis indicated that sacituzumab govitecan-hziy (Trodelvy) improved progression-free survival (PFS) and overall response rate (ORR) among patients with HER2-low or HER2 immunohistochemistry zero (IHC0), hormone receptor­–positive metastatic breast cancer in the phase 3 TROPiCS-02 trial (NCT03901339).

Frederik Marmé, MD, presented the findings during the ESMO 2022 Congress. “HER2-low is a relatively newly defined subpopulation of her to negative patients that has recently gained therapeutic interest,” he said. This subcategory accounts for approximately 65% of patients with HR-positive/HER2-negative breast cancer.

Patients with HER2-low disease assigned to sacituzumab govitecan had superior median PFS compared with physician’s choice of treatment (6.4 vs 4.2 months; HR, 0.58; 95% CI, 0.42-0.79; P < .001). PFS was similarly superior with sacituzumab govitecan in the IHC0 (5.0 vs 3.4 months; HR, 0.72; 0.51-1.00; P = .05) and intention-to-treat (ITT; 5.5 vs 4.0 months; HR, 0.66; 95% CI, 0.53-0.83; P = .0003) populations.

“This study demonstrated improved efficacy outcomes on sacituzumab govitecan vs [physician’s choice of treatment] in HER2-low as well as hormone receptor–positive, HER2-negative metastatic breast cancer. These results are consistent with the overall study results of TROPiCS-02 in the ITT population,” Marmé said. “Sacituzumab govitecan should be considered an effective treatment option for patients with HR-positive, HER2-negative metastatic breast cancer regardless of HER2 IHC status.”

Investigators in the TROPiCS-02 trial enrolled 543 patients who previously received taxane, endocrine therapy, CDK4/6 inhibitor, and 2 to 4 prior lines of chemotherapy. Patients were randomly assigned to 10 mg/kg sacituzumab govitecan on days 1 and 8 of a 21-day cycle or physician’s choice of treatment until progression or unacceptable toxicity.

For this retrospective subgroup analysis, investigators evaluated local IHC and in-situ hybridization to determine efficacy by HER IHC status.

Fifty-two percent of patients were HER2-low. Of those, 149 were assigned to sacituzumab govitecan and 134 to physician’s choice. Forty percent of patients were IHC0. Of those, 101 were assigned sacituzumab govitecan and 116 were assigned to physician’s choice. Forty-three patients were excluded from analysis due to missing IHC status.

ORR favored sacituzumab govitecan in the HER2-low (26% vs 12%; odds ratio [OR], 2.52; 95% CI, 1.33-4.78) and ITT (21% vs 14%; OR, 1.63; 95% CI, 1.04-2.55) populations. However, the antibody-drug conjugate (ADC) did not improve ORR in the IHC0 cohort (16% vs 15%; OR, 1.10; 95% CI, 0.52-2.30).

The median duration of response (DOR) in the HER2-low group was 7.4 months (95% CI, 5.8-8.9) vs 4.1 months (95% CI, 2.8-6.1) in favor of sacituzumab govitecan. Similarly, DOR was superior in the sacituzumab govitecan arms in the IHC0 (8.1 vs 6.1 months) and the ITT (7.4 vs 5.6 months) subgroups.

“The safety profile of sacituzumab govitecan in the HER2-low as well as HER2-zero subgroups was generally consistent with that of the overall TROPiCS-02 safety population,” Marmé said.

Shom Goel, MD, a consultant medical oncologist and group leader at the Peter MacCallum Cancer Centre, offered perspective on the findings. He noted that the difference between HER2-low and IHC0 is “very, very blurry.” He added that interpathology concordance separating IHC0 from IHC1 is “actually pretty bad.”

“As more and more ADCs come onto the market, targeting all kinds of different targets, we’re going to have to be really careful that we don’t get caught up chasing our tail trying to classify and reclassify breast cancer using very imperfect tools which do not have a biological basis,” he said.

Earlier in the conference, Hope S. Rugo, MD, director of Breast Oncology and Clinical Trials Education and professor of medicine in the Division of Hematology and Oncology at the UCSF Helen Diller Family Comprehensive Cancer Center, presented data showing that sacituzumab govitecan-hziy provided a clinically meaningful OS benefit for patients with pretreated hormone receptor–positive, HER2-negative metastatic breast cancer who were resistant to endocrine therapy. Sacituzumab govitecan induced a 3.2-month improvement in survival and a 21% relative reduction in the risk for death compared with physician’s choice of treatment.


Schmid P, Cortes J, Marmé F, et al. Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase 3 TROPiCS-02 study. Ann Oncol. 2022; 33(suppl 7):S88-S121. doi:10.1016/annonc/annonc1040

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