Trodelvy (sacituzumab govitecan) improved both progression-free and overall survival as well as quality of life compared with chemotherapy in people with triple-negative breast cancer (TNBC). These findings, from two different analyses of the ASCENT trial, were presented at the European Society for Medical Oncology (ESMO) Congress 2021.
Breast cancer is classified by the type of receptors tumor cells express. Most breast tumors have estrogen or progesterone receptors that make them suitable for hormone therapy, while others express a high level of HER2, a growth-promoting protein receptor. Triple-negative breast cancer doesn’t express any of these receptors and is harder to treat. Some 15% to 20% of patients with breast cancer have TNBC.
The ASCENT trial (ClinicalTrials.gov Identifier NCT02574455) is a global, randomized Phase III study with more than 500 patients recruited across 230 locations. They had inoperable locally advanced or metastatic TNBC and had received at least two prior systemic treatments.
The study assessed the efficacy and safety of Trodelvy compared with physician-recommended chemotherapy. Trodelvy is an antibody-drug conjugate that combines a monoclonal antibody targeting Trop-2, a protein found in many different epithelial cancers including 90% of TNBC, and a topoisomerase inhibitor chemotherapy drug. It was approved in 2020 for people with previously treated locally advanced or metastatic TNBC and in 2021 for patients with advanced bladder cancer.
For the first substudy, Javier Cortés, MD, of the International Breast Cancer Center in Barcelona and colleagues included 146 individuals who did not have TNBC when initially diagnosed with breast cancer and whose cancer had not spread to the brain.
“In the metastatic stage of breast cancer, it is not uncommon for people to change from one subtype to another,” Cortés said in a Gilead Sciences press release.
Of this group, 70 were randomly assigned to receive Trodely and 76 received physician-recommended chemotherapy, both by IV infusion.
The researchers found that people taking Trodelvy had an average progression-free survival time—a period without worsening of disease—of 4.6 months compared with 2.3 months for those on chemotherapy. The median overall survival time was 12.4 months versus 6.7 months, respectively. In addition, the overall response rate—meaning those who saw a reduction in tumor size—was 31% in the Trodelvy group versus 4% in the chemotherapy group. People taking Trodelvy were more likely to experience certain adverse events, including neutropenia, anemia and diarrhea, than those on chemotherapy.
“Roughly one-third of patients with TNBC in the ASCENT study were not originally diagnosed with TNBC, and they still experienced a survival benefit with Trodelvy compared with chemotherapy,” said Cortés. “For treating physicians, this reinforces Trodelvy’s efficacy in more complex patients.”
In the second analysis, Sibylle Loibl, MD, of Bethanien Hospital Frankfurt in Germany, and colleagues found that Trodelvy improved health-related quality of life for people with previouly treated TNBC. Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), health-related quality of life was evaluated at baseline, on the first day of each treatment cycle and when therapy ended. The questionnaire assessed individual perceptions of social, mental and physical health that are influenced by the disease as well as side effects of treatment.
In a study population of 419 patients, the 236 people who were randomly assigned to Trodelvy reported better health-related quality of life scores, including physical functioning, emotional functioning and global health status, comparison with the 183 people who received chemotherapy. Those on Trodelvy reported less pain, shortness of breath, insomnia and fatigue but experienced worse diarrhea.
“In TNBC, limited treatment options and poor survival outcomes are compounded by a significant decrease in quality of life, especially in relapsed or refractory metastatic disease, where patients can undergo many rounds of chemotherapy,” Loibl said in a press release. “Trodelvy is not only the first treatment to extend survival in these patients, but this analysis shows it can also significantly lessen the burden of symptoms when quality time is especially important.”