Treatment with Trodelvy resulted in slight survival improvements, when compared with standard of care chemotherapy regimens, in patients with hormone receptor–positive, HER2-negative metastatic breast cancer.
Findings from the phase 3 TROPiCS-02 trial demonstrated that the use of Trodelvy (sacituzumab govitecan-hziy) was associated with a benefit among hormone receptor–positive, HER2-negative breast cancer that was resistant to endocrine-based therapies.
The data — which were presented at the 2022 American Society of Clinical Oncology Annua Meeting — showed that versus a physician’s choice of standard of care chemotherapy, Trodelvy reduced the risk of disease progression by 34%.
At a median follow-up of 10.2 months, treatment with Trodelvy was associated with inducing a median progression-free survival (or time from the start of treatment until disease progression) of 5.5 months versus 4 months with the investigator’s choice of chemotherapy.
The overall survival (time a patient is alive with their disease) data were not mature at the time of the primary analysis; however, the study authors noted that there was a numeric trend toward improvement with Trodelvy versus standard of care chemotherapy.
“A subset of these heavily pretreated patients had rapid progression in the first two months on treatment,” lead study author Dr. Hope S. Rugo, director of Breast Oncology and Clinical Trials Education at UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, said during a press briefing on the data. “Therefore, we analyzed (progression-free survival) at several key landmark time points.”
Specifically, at six months, 46% of the 272 patients who received Trodelvy were alive without disease progression compared with 30% of the 271 patients who received chemotherapy. At 12 months the progression-free survival rates were 21% vs 7%, respectively.
“(Trodelvy) 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.
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. Because of acquired resistance, outcomes for patients who receive chemotherapy in later-line settings are not favorable with a progression-free survival of approximately 4 months.
Investigators of TROPiCS-02 evaluated the safety and efficacy of single-agent Trodelvy, 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.
Patients with hormone receptor–positive, HER2-negative metastatic breast cancer who were refractory to or relapsed after at least two prior systemic chemotherapy regimens for metastatic disease including at least one prior anticancer hormonal treatment and
at least one CDK4/6 inhibitor administered in the metastatic setting were enrolled onto the TROPiCS-02 trial.
Patients could not have received more than four prior lines of chemotherapy prior to enrollment. Investigators noted that therapy administered in the neoadjuvant (therapy delivered to help reduce size of tumor before the main treatment is given) or adjuvant (treatment given after primary therapy to prevent disease recurrence) setting for early-stage disease qualified as a prior line of chemotherapy if disease recurred within 12 months.
Patients were randomly assigned to receive Trodelvy or investigator’s choice of chemotherapy until disease progression or unacceptable toxicity occurred. The main focus of the study was to identify progression-free survival in the patient groups. The investigators also wanted to analyze overall survival, response to treatment, duration of response, quality of life and safety.
Most patients had liver metastases at time of enrollment (84% and 87%, respectively).
The median number of prior lines of chemotherapy in the metastatic setting was three (range, 0 to 8) for those who received Trodelvy and three (range, 1 to 5) for those who received chemotherapy.
In terms of safety, no new toxicity signals were observed with Trodelvy and were manageable based on observations in prior studies, according to Rugo. The most common side effects associated with Trodelvy were diarrhea and neutropenia (an abnormally low count of a type of white blood cells). Among the six deaths that occurred in the Trodelvy group, only one was attributed 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.
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