Episode 9: The TROPiCS-02 trial, final results on overall survival
The TROPiCS-02 trial represents an international, open-label, phase 3 investigation targeting patients with advanced hormone receptor-positive (HR-positive) and human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer. This study specifically focuses on individuals with advanced luminal disease who exhibited progression under endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, having received a minimum of two and a maximum of four prior chemotherapy treatments in the advanced setting.
Participants in the trial were randomly assigned in a 1:1 ratio to receive either sacituzumab govitecan (SG) or traditional chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine). The primary endpoint of interest was progression-free survival, as previously presented at the European Society for Medical Oncology (ESMO). While the positive outcome demonstrated a modest numerical increase of 1.5 months, it signifies a noteworthy improvement in efficacy, particularly in the late-line treatment setting.
Moreover, the study revealed a preference for SG over physician’s choice, as indicated by an overall response rate of 58% compared to 38%. The potential activity of SG is eagerly anticipated in terms of overall survival, with results presented at the American Society of Clinical Oncology (ASCO) by Dr. Tolaney.
The observed hazard ratio of 0.79 suggests a statistically significant increase in the overall survival of SG-treated patients by a median of 3.2 months compared to the physician’s choice of treatment. This benefit was consistently observed across all subgroup analyses, independent of the treatment line for CDK4/6 inhibition. Notably, a shorter treatment period below 12 months with CDK4/6 inhibitors resulted in a more pronounced overall survival benefit with SG. The limited inclusion of patients with very low TROP2 expression precludes definitive conclusions in this regard.
In summary, the conclusive outcomes of the TROPiCS-02 study pave the way for a novel treatment approach for patients previously subjected to endocrine and CDK4/6 inhibitor therapies, with a demonstrated advantage of SG over conventional chemotherapy. Considering the safety profile of SG aligns with prior reports, regulatory approval from the European Medicines Agency (EMA) has been granted. The impending reimbursement of SG in Belgium for this patient population appears imminent, given the substantial clinical improvement in overall survival among heavily pretreated individuals with unresectable, metastatic HR+/HER2- breast cancer.
References:
Rugo HS. et al. (2023) Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 402(10411): 1423-1433