Sacituzumab govitecan (1) – Trodelvy®

• Clinical trials
  • In the ASCENT trial, sacituzumab govitecan was compared with chemotherapy of the clinician’s choice, comprising the treatment options capecitabine, vinorelbine, eribulin or gemcitabine (each as monotherapy).

Adults with inoperable or metastatic triple-negative breast cancer (mTNBC) who have received at least two previous systemic therapies, at least one of which was for advanced disease

• In the overall assessment, sacituzumab govitecan is found to provide major additional benefit in adults with unresectable or metastatic triple-negative breast cancer who have previously received two or more systemic therapies, including at least one for advanced disease.
• The certainty of evidence for the established additional benefit is classified as an indication.
• mortality
  • For the endpoint of overall survival, there is a statistically significant difference in favour of sacituzumab govitecan compared with capecitabine, vinorelbine and eribulin.
  • The extent of the prolongation in overall survival achieved is assessed as a very clear improvement.
• Morbidity – Progression-free survival (PFS)
  • In the ASCENT trial, PFS 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.
  • The morbidity component was not assessed on the basis of symptoms, but exclusively by means of imaging procedures (radiologically determined disease progression according to the RECIST 1.1 criteria).
• Morbidity – Symptoms
  • Symptoms were assessed in the ASCENT study using the symptom scales of the cancer-specific EORTC QLQ-C30 questionnaire.
  • The assessment of symptoms was operationalised as the time to first deterioration. An increase in the score of ≥ 10 points compared with the start of the study was considered a clinically relevant deterioration.
  • With regard to the endpoints of nausea and vomiting, insomnia, loss of appetite and constipation, there was no statistically significant difference between the treatment arms in any case.
  • For the endpoints of fatigue, pain and dyspnoea, there was a statistically significant advantage in favour of sacituzumab govitecan compared with the appropriate comparator therapy.
  • With regard to the endpoint of diarrhoea, there was a statistically significant difference to the detriment of sacituzumab govitecan compared with capecitabine, eribulin and vinorelbine.
  • An overall assessment of the results reveals both advantages and a disadvantage for sacituzumab govitecan compared with the appropriate comparator therapy in terms of symptoms, although the positive effects of sacituzumab govitecan predominate overall.
• quality of life
  • Health-related quality of life was assessed in the ASCENT study 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.
  • For the endpoints of global health status, cognitive functioning and social functioning, there was no statistically significant difference between the treatment arms in any case.
  • With regard to the endpoints of physical functioning, role functioning and emotional functioning, a statistically significant advantage was observed in favour of 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 the ASCENT trial, adverse events occurred in almost all patients enrolled in both treatment arms. The results are presented here for supplementary information only.
• Side effects – Serious adverse events (SAEs)
  • For the SAE endpoint, there was a statistically significant difference in favour of sacituzumab govitecan compared with the appropriate comparator therapy.
• Side effects – Severe adverse events (CTCAE grade ≥ 3) and discontinuation due to adverse events (AEs)
  • With regard to the endpoints of severe AEs and discontinuation due to AEs, there was no statistically significant difference between the treatment arms in either case.
• Overall assessment
  • For the benefit assessment of sacituzumab govitecan for the treatment of unresectable or metastatic triple-negative breast cancer, in adults who have previously received two or more systemic therapies, including at least one directed against the advanced disease, data are available from the ASCENT trial for the relevant patient population on mortality, morbidity, quality of life and side effects.
  • For the endpoint of overall survival, there is a statistically significant difference in favour of sacituzumab govitecan compared with capecitabine, eribulin or vinorelbine. The extent of the effect is assessed as a very marked improvement.
  • With regard to symptoms, the EORTC QLQ-C30 shows several advantages as well as one disadvantage for sacituzumab govitecan compared with the appropriate comparator therapy.
  • In terms of quality of life, the EORTC QLQ-C30 shows exclusively positive effects for sacituzumab compared with the appropriate comparator therapy.
  • For the ‘side effects’ endpoint category, an advantage for sacituzumab govitecan over capecitabine, eribulin or vinorelbine can be observed for SAE, as well as specific advantages and disadvantages for particular AEs. In the overall assessment of adverse event endpoints, the positive effects of sacituzumab govitecan predominate.
  • Overall, sacituzumab govitecan is found to offer a significant improvement in treatment-related benefit compared with the appropriate comparator therapy – a level of improvement not previously achieved – particularly given the severity of triple--negative breast cancer and the poor prognosis of patients, who, moreover, are already at a late stage of treatment within the indicated therapeutic indication.

Courtesy translation only, please refer to the German original.