Gozetotide is a drug for diagnostic application in adults with prostate cancer. It is currently the only diagnostic agent that recognizes PSMA-positive prostate cancer and can therefore identify patients for whom PSMA-targeted therapy with (177Lu)lutetium vipivotide tetraxetan (“Lutetium-177” for short) is an option.
In an early benefit assessment, the Institute for Quality and Efficiency in Health Care (IQWiG) has now investigated whether gozetotide (possibly with subsequent lutetium-177 therapy) offers an added benefit for men with metastatic, castration-resistant prostate cancer over individualized treatment without determination of the PSMA status (and therefore without the use of PSMA-targeted therapy).
A study for the assessment of the diagnostic and therapeutic agents
The abbreviation PSMA stands for prostate-specific membrane antigen: a protein that can occur in increased amounts on cancer cells. Lutetium-177 is a radioactive substance that binds to PSMA and can thus irradiate the cancer cells in a targeted manner. The aim is to slow down cancer growth and alleviate symptoms. Gozetotide is used for diagnostics prior to treatment with lutetium-177. Gozetotide also binds to the cancer cells that carry PSMA on their surface. It is radioactively labelled and thus visualizes the cancer cells during a PET scan.
The health-related benefits or harms of diagnostic tests are essentially only realized through the subsequent therapeutic or preventive procedures. Gozetotide is the only approved diagnostic agent for the detection of PSMA-positive changes in patients with prostate cancer. Therefore, it does not replace any other test, but recognizes a new type of disease (PSMA-positive prostate cancer) for which an effective therapy is available (Lutetium-177). By linking diagnostics and therapy, the same VISION study can be used for the early benefit assessment of the diagnostic agent gozetotide as for the existing one of the therapeutic agent lutetium-177. The pharmaceutical company's updated search showed that, despite the time lag between the VISION study and the benefit assessment of the therapeutic agent lutetium-177, no further evidence on gozetotide (followed by lutetium-177) is currently available in addition to the VISION study.
Statements on added benefit only possible for certain patients
The VISION study is an unblinded, randomized controlled trial with an enrichment design that included 831 men with PSMA-positive prostate cancer, each after PSMA diagnostics with gozetotide. All patients in the VISION study received hormone blockade and individually adapted treatment. 551 men were additionally treated with lutetium-177. The androgen receptor pathway inhibitors enzalutamide and abiraterone were, among other drugs, administered as individually adapted treatment; cabazitaxel and olaparib were not permitted. Thus, the comparator therapies used in the study did not cover all treatment options available for individualized treatment in the therapeutic indication. Consequently, the VISION study only allows conclusions on the added benefit of gozetotide in those patients for whom abiraterone in combination with prednisone or prednisolone, enzalutamide or best supportive care is the most suitable individualized treatment.
The study suggests an advantage for Lutetium-177 after PSMA diagnostics with gozetotide, particularly in terms of overall survival. Furthermore, there were also positive effects for the study outcomes "spinal cord compression" and "need for radiotherapy for alleviation of bone pain". Although severe side effects such as myelosuppression also occurred, these do not call into question the benefits for patients.
Overall, the assessment result corresponds to the early benefit assessment of lutetium-177 from July 2023: There is a major added benefit of gozetotide over the appropriate therapy for patients for whom abiraterone (with prednisone or prednisolone), enzalutamide or best supportive care is the best therapy. The added benefit is not proven in patients for whom cabazitaxel or olaparib is the best choice, as these therapies were not permitted in the study.
The G-BA decides on the extent of added benefit
The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.