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Sacituzumab govitecan elicited a statistically significant and clinically meaningful benefit among patients with hormone receptor–positive, HER2-negative breast cancer with endocrine therapy resistance, reducing the risk of disease progression by 34% vs standard chemotherapy, according to results of the phase 3 TROPiCS-02 trial.
Sacituzumab govitecan-hziy (Trodelvy) elicited a statistically significant and clinically meaningful benefit among patients with hormone receptor–positive, HER2-negative breast cancer with endocrine therapy resistance, reducing the risk of disease progression by 34% vs standard chemotherapy, according to results of the phase 3 TROPiCS-02 trial (NCT03901339) presented at the 2022 ASCO Annual Meeting.1
At a median follow-up of 10.2 months, the median progression-free survival (PFS) was 5.5 months (95% CI, 4.2-7.0) with sacituzumab govitecan vs 4.0 months (95% CI, 3.1-4.4) with investigator’s choice chemotherapy (HR, 0.66; 95% CI, 0.53-0.83; P < .0003). The overall survival (OS) data were not mature at the time of the primary analysis; however, investigators noted a numeric trend toward improvement with the antibody-drug conjugate vs standard care.
“A subset of these heavily pretreated patients had rapid progression in the first 2 months on treatment,” Hope S. Rugo, MD, FASCO, said during a press briefing on the data. “Therefore, we analyzed PFS at several key landmark time points. The Kaplan-Meier curves separated early and were consistent over time with a higher proportion of patients alive and progression free at all landmark time points.”
Specifically, at 6 months, 46% of patients who received sacituzumab govitecan (n = 272) were alive without worsening disease compared with 30% who received chemotherapy (n = 271). At 12 months the PFS rates were 21% vs 7%, respectively.
“Sacituzumab govitecan demonstrated significant clinical benefit and manageable safety compared with chemotherapy in patients with heavily pretreated, endocrine-resistant hormone receptor–positive, HER2-negative advanced breast cancer, and should be considered a potential treatment in this heavily pretreated population,” said Rugo, who is a professor of medicine and director, breast oncology and clinical trials education at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.
For patients who develop progressive disease following sequential treatment with endocrine therapies, including CDK4/6 inhibitors, mTOR inhibitors, and PI3K inhibitors, the standard of care consists of single-agent chemotherapy such as capecitabine, vinorelbine, gemcitabine or eribulin.1,2 Because of acquired resistance, outcomes for patients who receive chemotherapy in later-line settings are not favorable with a PFS of approximately 4 months.2
Investigators of TROPiCS-02 evaluated the safety and efficacy of single-agent sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, a calcium signal transducer, which is highly expressed in hormone receptor–positive, HER2-negative breast cancer compared with other subtypes.2 The agent comprises a humanized anti–Trop-2 monoclonal antibody with an SN-38 payload attached via a proprietary hydrolyzable linker.2
TROPiCS-02 enrolled patients with hormone receptor–positive, HER2-negative metastatic breast cancer who were refractory to or relapsed after at least 2 prior systemic chemotherapy regimens for metastatic disease including at least 1 prior anticancer hormonal treatment and at least 1 CDK4/6 inhibitor administered in the metastatic setting.
Patients could not have received more than 4 prior lines of chemotherapy prior to enrollment. Investigators noted that therapy administered in the neoadjuvant or adjuvant setting for early-stage disease qualified as a prior line of chemotherapy if disease recurred within 12 months. Further, patients must have had measurable disease per RECIST 1.1 criteria.1,3
Patients were randomly assigned 1:1 to receive sacituzumab govitecan at 10 mg/kg via intravenous infusion on days 1 and 8 of a 21-day cycle or investigator’s choice chemotherapy until progression or unacceptable toxicity. The primary end point was PFS with secondary end points including OS, response, duration of response, quality of life, and safety. Stratification factors included the following: visceral metastases (yes vs no), endocrine therapy in metastatic setting for at least 6 months (yes vs no), and prior lines of chemotherapies (2 vs 3-4).1
Baseline characteristics were well balanced between the 2 arms. The median age in the investigative arm was 57 years (range, 29-86) and 55 years (range, 27-78) in the control arm. Most patients had liver metastases at baseline (84% and 87%, respectively), had an ECOG performance status of 1 (57% and 54%), and had received a prior CDK4/6 inhibitor within 12 months (59% and 61%).1
The median number of prior lines of chemotherapy in the metastatic setting was 3 (range, 0-8) for those who received sacituzumab govitecan and 3 (range, 1-5) for those who received chemotherapy.
In terms of safety, no new toxicity signals were observed in with sacituzumab govitecan and were manageable based on observations in prior studies. The most common adverse effects were diarrhea and neutropenia. Among the 6 deaths reported in the sacituzumab govitecan arm, 1 was related to treatment.
“No other specific pattern was identified following detailed review of all safety events leading to death,” Rugo said, noting that other events included COVID-19 infection, pneumonia, and other illnesses.