Lutetium (177Lu) Vipivotidtetraxetan (1) – Pluvicto®

• Clinical trials
  • The VISION trial is an open-label, randomised, controlled Phase III trial in which (177Lu) lutetium vipivotid tetraxetan is compared with the continuation of existing androgen deprivation therapy (ADT) and patient-specific therapy, versus the continuation of existing ADT and patient-specific therapy alone.

a1) Adults with PSMA-positive, metastatic, castration-resistant prostate cancer (mCRPC), following prior treatment with ARDT (androgen receptor-directed therapy) and taxane-based chemotherapy - Adults for whom abiraterone in combination with prednisone or prednisolone, enzalutamide or best supportive care represents the most appropriate treatment on an individual basis

• Indication of a considerable additional benefit
• Consequently, the G-BA has determined that (177Lu) lutetium vipivotid tetraxetan, in combination with ADT and patient-specific therapy, offers a considerable amount of additional benefit for patients with previously treated mCRPC compared with ADT in combination with patient-specific therapy.
• Consequently, the certainty of the evidence for the established 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 and was recorded as the sole endpoint until the end of the trial.
  • For this endpoint, a statistically significant survival benefit in favour of the patient population that was randomized on or after 5 March 2019 (177Lu) lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy.
  • 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, as determined by blinded, independent and central assessment in accordance with the PCWG3 criteria, or death from any cause.
  • With (177Lu) 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 endpoint rPFS under consideration is a composite endpoint comprising endpoints from the ‘mortality’ and ‘morbidity’ categories.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint to patients. The overall conclusion regarding additional benefit remains unaffected.
• 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: A new symptomatic pathological fracture, spinal cord compression, tumour-related orthopaedic surgery, or the need for radiotherapy to relieve bone pain.
  • The results for the composite endpoint of symptomatic skeletal-related events, based on patients randomised from 5 March 2019 onwards, can be considered.
  • For the individual components of spinal cord compression and the need for radiotherapy to relieve bone pain, a statistically significant advantage was observed in favour of (177Lu) lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy.
  • For the individual endpoints of new symptomatic 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 (177Lu) lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy.
• Health-related quality of life – FACT-P
  • For the health-related quality of life endpoint, assessed using the FACT-P, the differential proportion of patients excluded from the analysis between the treatment arms is, for both the patient population (patients randomised from 5 March 2019) and the overall population (all randomised patients) > 15 percentage points. Consequently, no suitable data are available.
• Side effects – severe adverse events (CTCAE grade ≥ 3)
  • For the endpoints ‘severe adverse events’ (CTCAE grade ≥ 3) and ‘withdrawal due to adverse events’, no statistically significant difference was observed between the treatment groups in either case.
• Overall assessment
  • For the assessment of the additional benefit of (¹⁷⁷Lu) lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy in patients with metastatic castration-resistant prostate cancer following at least two prior treatments, results are available on mortality, morbidity, health-related quality of life and side effects from the open-label, randomised, controlled Phase III VISION trial.
  • With the data on patients randomised from 5 March 2019 onwards, which were submitted during the commenting procedure, a patient population that is largely analysable has been identified alongside the overall population, as the difference in the proportion of patients who did not receive study medication between the treatment arms is < 15 percentage points.
  • For the endpoint of overall survival, a clear advantage in favour of (177Lu) lutetium vipivotidtetraxetan in combination with ADT and patient-specific therapy.
  • In the morbidity category, treatment with (177Lu) lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy shows clear advantages for patients in the patient population when considering the composite endpoint of symptomatic skeletal-related events (SSREs).
  • No suitable data are available for the endpoints of pain (assessed using the BPI-SF) and health status (assessed using the EQ-5D VAS).
  • No suitable data are available for health-related quality of life (assessed using the FACT-P).
  • For the endpoint category of side effects, an overall advantage can be identified for (177Lu) lutetium vipivotid tetraxetan in combination with ADT and patient-specific therapy compared with ADT in combination with patient-specific therapy in the patient population, due to the avoidance of SUEs. In detail, both advantages and disadvantages are evident for individual specific adverse events.
  • Overall, positive effects are observed 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.

a2) Adults with PSMA-positive, metastatic, castration-resistant prostate cancer (mCRPC), following prior treatment with ARDT (androgen receptor-directed therapy) and taxane-based chemotherapy - Adults for whom cabazitaxel or olaparib represents the most appropriate treatment on an individual basis

• An additional benefit is not proven.
• The available data do not allow conclusions to be drawn regarding additional benefit for patients for whom cabazitaxel or olaparib is the individually appropriate treatment.
• For the treatment of adult men with metastatic castration-resistant prostate cancer following prior treatment with ARDT and taxane-based chemotherapy, for whom cabazitaxel or olaparib is the individually appropriate therapy, additional benefit is not proven.

Courtesy translation only, please refer to the German original.