177Lu-PSMA-617 for treatment of metastatic castration resistant prostate cancer: a health technology assessment
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177Lu-PSMA-617 is a new radioligand therapy that is being used in treating metastatic castration resistant prostate cancer. It consists of the radionuclide lutetium-177 labelled with the ligand PSMA-617 for specific binding to prostate-specific membrane antigen (PSMA) typically expressed by prostate cancer cells. In this health technology assessment, we included three randomised controlled trials that compared the effect of 177LuPSMA-617, either alone or in combination with standard of care therapy (SoC), to docetaxel, cabazitaxel, or SoC alone. The main efficacy outcome was survival, i.e., overall survival (OS), as well as progression-free survival (PFS). Safety outcome was severe adverse events ≥grade 3 (SAE). The results are presented as hazard ratio (HR) and risk ratio (RR), with an assessment of our conficence in the results (GRADE). 177Lu-PSMA-617 + SoC versus SoC alone (total n=831) - OS: HR 0.62 (0.52 to 0.74) (GRADE: high) - PFS: HR 0.40 (0.31 to 0.51) (GRADE: high) - SAE: RR 1.39 (1.14 to 1.69) (GRADE: moderate) 177Lu-PSMA-617 versus cabazitaxel (total n=200) - PFS: HR 0.63 (0.46 to 0.86) (GRADE: low) - SAE: RR 0.73 (0.18 to 1.04) (GRADE: very low) 177Lu-PSMA-617 versus docetaxel (total n=40) - PFS: HR 0.90 (0.46 to 1.77) (GRADE: very low) - SAE: RR 0.60 (0.27 to 1.34) (GRADE: very low) Treatment with 177Lu-PSMA-617 plus SoC therapy prolonged overall and progression-free survival with median four and five months, respectively, compared with SoC alone, but increased the risk of severe adverse events ≥grade 3 in patients previously treated with hormone therapy and taxane-based chemotherapy. We have high and moderate confidence in these results. 177LuPSMA-617 prolonged progression-free survival and reduced the risk of severe adverse events ≥3 more than cabazitaxel in patients previously treated with docetaxel. However, we have low and very low confidence in these results. There is seemingly no difference in progression-free survival when comparing 177Lu-PSMA-617 with docetaxel in patients who were treatment-naïve, but 177LuPSMA-617 reduced the risk of severe adverse events ≥3 more than docetaxel. However, we have very low confidence in these results. The most common adverse events associated with 177Lu-PSMA617 were fatigue, dry eyes and mouth, and pain. The incidence of more serious adverse events such as nephrotoxicity, was low. Patients’ expectation towards 177Lu-PSMA-617 is first and foremost as a new option for life prolonging treatment for mCRPC. An implementation of 177Lu-PSMA-617 in Norway will likely affect the current organisation and allocation of resources. Furthermore, implementation must ensure that the treatment is managed in line with the Norwegian radiation protection legislation. Our cost-effectiveness analysis shows that treatment with 177LuPSMA-617 together with SoC is more effective, but also more costly than SoC alone in mCRPC patients who previously have been treated with anti-androgen therapy and taxane-based chemotherapy. The incremental cost-effectiveness ratio (ICER) was NOK XX XXXXX per quality adjusted life year (QALY). The absolute shortfall for patients with mCRPC is equal to 11.67 QALYs.