Gozetotid (1) – Locametz®

• Clinical trials
  • To demonstrate the additional benefit of gozetotid in detecting prostate-specific membrane antigen (PSMA)-positive lesions in patients with PSMA-positive, progressive, metastatic, castration-resistant prostate cancer (mCRPC), for whom PSMA-targeted therapy is indicated, the pharmaceutical manufacturer has submitted the results of the VISION trial.
  • The VISION study is an open-label, randomised, controlled Phase III trial in which, following diagnosis with gozetotid, PSMA-positive patients were treated with (Lu)lutetium vipivotide tetraxetan whilst continuing their existing androgen deprivation therapy (ADT) and patient-specific treatment, compared with continuing existing ADT and patient-specific treatment alone.

a1) Adults with progressive, metastatic, castration-resistant prostate cancer (mCRPC); Diagnosis; identification of patients with prostate-specific membrane antigen (PSMA)-positive, progressive, metastatic, castration-resistant prostate cancer (mCRPC) for whom PSMA-targeted therapy is indicated - Adults for whom abiraterone in combination with prednisone or prednisolone, enzalutamide or best supportive care represents the most appropriate treatment on an individual basis

• Overall, there is an indication of considerable additional benefit for gozetotid (possibly followed by (Lu)lutetium vipivotid tetraxetan in combination with ADT and a patient-specific treatment regimen).
• Consequently, the certainty of the evidence for the identified additional benefit is classified as ‘indication’.
• mortality
  • In the VISION trial, overall survival was defined as the time (in months) between randomisation and death from any cause.
  • For the endpoint of overall survival, a statistically significant survival benefit in favour of the patient population that was randomized on or after 5 March 2019 (Lu)lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy following PSMA diagnosis with gozetotid.
  • The extent of the prolongation in overall survival achieved is considered a significant improvement.
• Morbidity – Radiographic progression-free survival (rPFS)
  • In the VISION trial, radiographic progression-free survival (rPFS) was defined as the time (in months) between randomisation and radiographic disease progression, based on blinded, independent and central assessment in accordance with the PCWG3 criteria, or death from any cause.
  • With (Lu)lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy, rPFS in the overall population is statistically significantly prolonged compared with ADT in combination with patient-specific therapy.
  • The rPFS endpoint in question is a composite endpoint comprising endpoints from the ‘mortality’ and ‘morbidity’ categories.
• Morbidity – Symptomatic skeletal-related events (SSRE)
  • The composite endpoint of symptomatic skeletal-related events was defined in the VISION study as the time (in months) between randomisation and the occurrence of any of the following events: - New symptomatic pathological bone fracture - Spinal cord compression - Tumour-related orthopaedic surgery - Need for radiotherapy to relieve bone pain
  • For the individual components of spinal cord compression and the need for radiotherapy to relieve bone pain, a statistically significant advantage was observed for (Lu)lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy following PSMA diagnosis with gozetotid.
  • For the individual components ‘new symptomatic pathological bone fracture’ and ‘tumour-related orthopaedic surgery’, no statistically significant difference was observed between the treatment groups.
  • For the present assessment, the result for the combined endpoint is used, which demonstrates a clear advantage of (Lu)lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy following PSMA diagnosis with gozetotid.
• Health-related quality of life
  • The health-related quality of life endpoint was assessed using the FACT-P.
  • Due to the high proportion of patients excluded from the analyses between the treatment groups in the patient population (patients randomised from 5 March 2019 onwards) as well as in the overall population, the analyses of quality of life are not included in the present benefit assessment. Consequently, no suitable data are available.
• Side effects – Adverse events (AEs)
  • In the control arm, 86% of patients experienced an adverse event, whilst in the intervention arm, an adverse event was observed in 99% of patients.
• Overall assessment
  • For the benefit assessment of gozetotid, which, following radiolabelling with gallium-68, is indicated for the detection of prostate-specific membrane antigen (PSMA)-positive lesions by positron emission tomography (PET) in adults with prostate cancer (PCa) to identify patients with PSMA-positive, progressive, metastatic, castration-resistant prostate cancer (mCRPC) for whom PSMA-targeted therapy is indicated, results on mortality, morbidity, health-related quality of life and side effects from the open-label, randomised, controlled Phase III VISION trial.
  • With regard to overall survival, there is a clear advantage in favour of (Lu)lutetium vipivotide tetraxetan in combination with ADT and patient-individualised therapy following PSMA diagnosis with gozetotid, both in the overall population and in the patient population.
  • In the morbidity category, there are clear advantages for patients in the patient population receiving treatment with (Lu)lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy following PSMA diagnosis with gozetotid.
  • For the endpoint category of side effects, (Lu)lutetium vipivotid tetraxetan in combination with ADT and patient-individualised therapy following PSMA diagnosis with gozetotid, compared with ADT in combination with patient-individualised therapy, an overall advantage was observed in the patient population due to the avoidance of SUEs.
  • Overall, positive effects are evident in the endpoint categories of mortality and morbidity. No suitable data are available for the endpoint category of health-related quality of life. An overall advantage is also observed in the endpoint category of side effects. Consequently, the G-BA identifies a considerable additional benefit for gozetotid (followed, where appropriate, by (Lu)lutetium vipivotid tetraxetan in combination with ADT and a patient-specific therapy) compared with the appropriate comparator therapy.

a2) Adults with progressive, metastatic, castration-resistant prostate cancer (mCRPC); Diagnostics; identification of patients with prostate-specific membrane antigen (PSMA)-positive, progressive, metastatic, castration-resistant prostate cancer (mCRPC) for whom PSMA-targeted therapy is indicated - Adults for whom cabazitaxel or olaparib represents the appropriate treatment on an individual basis

• The additional benefit is not proven.
• The available data do not allow conclusions to be drawn regarding additional benefit for adults for whom cabazitaxel or olaparib constitutes the individually appropriate therapy, as neither cabazitaxel nor olaparib was used as part of individually tailored therapy. An additional benefit of gozetotid (followed, where appropriate, by (Lu)lutetium vipivotid tetraxetan in combination with ADT and a patient-specific therapy) is not proven for patients for whom cabazitaxel or olaparib is the appropriate patient-specific therapy.

Courtesy translation only, please refer to the German original.