CADTH Reimbursement Recommendation - Lutetium ( 177 - Lu) Vipivotide Tetraxetan (Pluvicto)

This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada. [...] • Ethical considerations arising in the evidence used to evaluate 177Lu vipivotide tetraxetan highlight limitations related to the definition of standard of care used in the VISION trial, whether the inclusion and exclusion criteria were adequately applied, and the high withdrawal rate from the control arm. [...] However, withdrawal rates in the BSC-BSoC group were 56.0% and 16.3% before and after the protocol amendment (respectively), compared with 1.2% and 4.2% in the 177Lu vipivotide tetraxetan group (i.e., although the rate of discontinuation from the BSC-BSoC group improved after the protocol amendment, it remained considerably higher than the rate observed in 177Lu vipivotide tetraxetan group). [...] This approach was acceptable to the FDA and Health Canada; however, both regulatory agencies stated that the interpretation of the magnitude of the rPFS effect was limited due to a high degree of censoring from early dropout in the control arm (neither the approved US label nor the product monograph in Canada included the effect size for rPFS from the VISION trial). [...] As with the VISION trial, the internal validity of the TheraP trial was limited by the high and disproportionate early dropout in the comparator group (15.8% in the cabazitaxel group versus 1.0% in the 177Lu vipivotide tetraxetan group withdrew before receiving any doses of the study medications).