The US FDA approved the ADC drug gosatumumab (Trodelvy) for the treatment of patients with hormone receptor-positive, HER2-negative breast cancer. In the trial, the drug significantly extended the overall survival of patients and reduced the risk of death by 21%.
Recently, the US FDA has approved the ADC drug Sacituzumab Govitecan-hziy (gosatuzumab, Trodelvy) for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer who have received endocrine therapy and at least 2 other systemic treatments following metastasis. Notably, gosatumumab (Trodelvy) is the first antibody-coupled drug (ADC) approved to treat this group of patients.
Basis for approval.
The approval is based on data from the Phase III TROPiCS-02 trial.
This global, multi-centre, open-label TROPiCS-02 trial enrolled 543 patients with hormone receptor-positive, HER2-negative metastatic breast cancer who had received prior endocrine therapy, CDK4/6 inhibitors and 2nd to 4th line chemotherapy.
Enrolled patients were randomised into two groups: one group received intravenous gosatumumab (Trodelvy); the other received physician's choice of eribulin, capecitabine, gemcitabine or vincristine chemotherapy alone.
Data from the trial showed that gosatumumab (Trodelvy) significantly prolonged the overall survival of patients compared to physician-selected chemotherapy alone. In the gosatumumab (Trodelvy) arm, patients had an average overall survival of 14.4 months compared to 11.2 months in the chemotherapy arm. This means that gosatumumab (Trodelvy) reduced the risk of death for patients by 21%.
In addition, the average length of time that patients in the gosatumumab (Trodelvy) group remained free of disease progression was 5.5 months compared to 4.0 months for chemotherapy. This means that gosatumumab (Trodelvy) reduced the risk of disease progression or death by 34%. The proportion of patients who remained free of disease progression for 1 year was 21% in the gosatumumab (Trodelvy) group, compared to 7% in the chemotherapy group.
Additional data presented at ESMO 2022 showed that 21% of patients in the gosatumumab (Trodelvy) arm had significant tumour shrinkage, compared to 14% in the chemotherapy arm. The average duration of treatment in the gosatumumab (Trodelvy) group was 8.1 months, compared to 5.6 months in the chemotherapy group.
In terms of safety, the results of TROPiCS-02 were consistent with previous gosatumumab (Trodelvy) studies, with no new safety signals identified in this patient group. Common serious adverse reactions included diarrhoea, febrile neutropenia, neutropenia, abdominal pain, colitis, neutropenic colitis, pneumonia and vomiting.
"Although some progress has been made in related research in recent years, new treatment options are still needed for patients with treated hormone receptor-positive, HER2-negative metastatic breast cancer. This is because almost all patients with this type of breast cancer assemble resistance to endocrine therapy and disease progression after existing chemotherapy treatment." Hope S. Rugo, principal investigator of the TROPiCS-02 trial and Director of Breast Oncology and Clinical Trials Education at the UCSF Comprehensive Cancer Center, said. "This approval is significant for the breast cancer patient population, where patients who have received endocrine therapy and chemotherapy have very limited treatment options, and the survival benefit and quality-of-life benefit of this trial over three months was unexpected."
