Sacituzumab govitecan (2) – Trodelvy®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted the results of the open-label, randomised, multicentre Phase III TROPiCS-02 trial.
  • In the TROPiCS-02 trial, sacituzumab govitecan was compared with treatment as prescribed by the doctor, with a choice of capecitabine, eribulin, gemcitabine or vinorelbine.
  • The EVER-132-002 study is an ongoing, open-label, randomised and controlled trial in which sacituzumab govitecan is being compared with treatment at the clinician’s discretion, with a choice of capecitabine, eribulin, gemcitabine and vinorelbine.

Adults with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have previously received endocrine-based therapy and at least two additional systemic therapies in the advanced stage

• Overall, sacituzumab govitecan is found to provide a significant and consistent improvement in health-related quality of life compared with the appropriate comparator therapy, particularly given the poor prognosis of patients who, in this therapeutic indication, are already at a late, palliative care setting.
• Furthermore, advantages are evident in terms of overall survival and morbidity. These are offset by disadvantages relating to side effects. Consequently, sacituzumab govitecan is found to offer considerable additional benefit compared with capecitabine, eribulin or vinorelbine.
• The certainty of the evidence for the established additional benefit is classified as ‘indication’.
• Overall, there is an indication of considerable additional benefit of sacituzumab govitecan compared with the appropriate comparator therapy.
• mortality
  • In both the TROPiCS-02 and EVER-132-002 studies, overall survival was defined as the time from randomisation to death, regardless of the underlying cause of death.
  • For the endpoint of overall survival, the meta-analysis of the studies shows a statistically significant advantage for sacituzumab govitecan compared with capecitabine, eribulin or vinorelbine.
• Morbidity – Progression-free survival (PFS)
  • PFS was the primary endpoint in both studies and was defined as the time from randomisation to the first observation of objective tumour progression or to death, whichever occurred first.
  • There was a statistically significant prolongation of PFS in favour of sacituzumab govitecan compared with the appropriate comparator therapy.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
• Health-related quality of life
  • Health-related quality of life was assessed in both studies using the functional scales of the cancer-specific EORTC QLQ-C30 questionnaire.
  • Quality of life was operationalised as time to first deterioration. A decrease in the score of ≥ 10 points compared with baseline was considered a clinically relevant deterioration.
  • There was no statistically significant difference between the treatment arms for the social functioning endpoint.
  • With regard to the endpoints of global health status, physical functioning, cognitive functioning, role functioning and emotional functioning, a statistically significant advantage was observed in each case for sacituzumab govitecan compared with capecitabine, eribulin and vinorelbine.
  • Overall, there were exclusively positive effects for sacituzumab govitecan in terms of quality of life.
• Side effects – Total adverse events (AEs)
  • In both studies, adverse events occurred in all study arms among almost all patients included.
• Overall assessment
  • A meta-analysis is available to assess the additional benefit of sacituzumab govitecan for the treatment of unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer in adults who have received endocrine-based therapy and at least two additional systemic therapies for advanced disease, a meta-analysis of the relevant patient population provides results for the endpoint categories of mortality, morbidity, health-related quality of life and side effects.
  • For the endpoint of overall survival, the meta-analysis of the studies shows a statistically significant advantage for sacituzumab govitecan compared with capecitabine, eribulin or vinorelbine.
  • With regard to morbidity, symptoms were assessed in the meta-analysis using the EORTC-QLQ-C30, and general health status was assessed using the visual analogue scale of the EQ-5D, both as reported by patients. The results show a statistically significant advantage for sacituzumab govitecan compared with capecitabine, eribulin or vinorelbine for health status. With regard to symptoms, there were more positive than negative effects. In the overall assessment of the results for the morbidity endpoint category, the positive effects predominate, such that an overall advantage of sacituzumab govitecan compared with the appropriate comparator therapy is inferred with regard to morbidity.
  • With regard to quality of life, the EORTC QLQ-C30 shows exclusively positive effects for sacituzumab govitecan compared with the appropriate comparator therapy. Findings on quality of life are of particular importance in the present palliative care setting.
  • For the endpoint category of AEs, a disadvantage for sacituzumab govitecan compared with capecitabine, eribulin or vinorelbine can be identified in terms of severe AEs, as well as specific advantages and disadvantages for individual AEs. In the overall assessment of adverse event endpoints, the negative effects of sacituzumab govitecan predominate.
  • Overall, sacituzumab govitecan is found to provide a clear and consistent improvement in health-related quality of life compared with the appropriate comparator therapy, particularly given the poor prognosis of patients who, in this therapeutic indication, are already at a late stage and palliative care setting. Furthermore, advantages are evident in terms of overall survival and morbidity. These are offset by disadvantages relating to side effects. Consequently, sacituzumab govitecan is found to offer considerable additional benefit compared with capecitabine, eribulin or vinorelbine.

Courtesy translation only, please refer to the German original.