Relugolix (1) – Orgovyx®

• Clinical trials
  • The HERO trial was an open-label, randomised, controlled Phase III trial comparing relugolix with leuprorelin, which was conducted between April 2017 and November 2021 at 160 centres in Asia, Australia, Europe, North and South America, involving a total of 1,078 patients.

a) Patients with advanced hormone-sensitive prostate cancer who are eligible for local therapy

• An additional benefit is not proven.
• For the treatment of adult men with advanced hormone-sensitive prostate cancer who are eligible for local therapy, the pharmaceutical manufacturer has not provided any data for the assessment of additional benefit. Consequently, additional benefit is not proven.

b) Patients with advanced hormone-sensitive prostate cancer who are not eligible for local therapy

• On balance, it is therefore concluded that, for relugolix in the treatment of patients with advanced hormone-sensitive prostate cancer who are not eligible for local therapy, an additional benefit is not proven compared with leuprorelin.
• mortality
  • In the HERO trial, the endpoint of overall survival was defined as the time from randomisation to death from any cause. No statistically significant difference was observed between the treatment groups.
  • With regard to overall survival, therefore, the additional benefit of relugolix compared with leuprorelin is not proven.
• Morbidity – Symptoms
  • Symptoms were assessed using the EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires.
  • For the endpoint of diarrhoea, as assessed using the EORTC QLQ-C30, a statistically significant disadvantage was observed compared with leuprorelin for relugolix. For all other symptom-related endpoints assessed using the EORTC QLQ-C30 and EORTC QLQ-PR25, no statistically significant difference was observed between the treatment groups.
• Morbidity – Health status
  • Health status was assessed using the visual analogue scale (VAS) of the EQ-5D questionnaire.
  • For this endpoint, no statistically significant difference was observed between the treatment groups.
• Health-related quality of life
  • Health-related quality of life was assessed using the EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires.
  • No suitable data are available for the endpoint ‘incontinence aids’ as assessed by the EORTC QLQ-PR25. For all other health-related quality of life endpoints assessed using the EORTC QLQ-C30 and EORTC QLQ-PR25, no statistically significant difference was observed between the treatment groups.
• Side effects – serious adverse events (SUEs), severe adverse events, discontinuation due to adverse events
  • For the endpoints SUEs, severe AEs (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥ 3) and discontinuation due to AEs, no statistically significant differences were observed between the treatment groups.
• Side effects – Major Adverse Cardiovascular Event (MACE)
  • For the composite endpoint MACE, a statistically significant difference in favour of relugolix over leuprorelin was observed when considering either SUE alone or severe AEs alone.
  • With regard to the MACE endpoint, although the pharmaceutical manufacturer’s statement has resolved various uncertainties regarding the measurability of this endpoint that were addressed in the IQWiG’s benefit assessment, other uncertainties remain.
  • In view of the lack of adjudication, no advantage of relugolix over leuprorelin can therefore be inferred.
• Overall assessment / Conclusion
  • For the assessment of the additional benefit of relugolix over leuprorelin in patients with advanced hormone-sensitive prostate cancer who are not eligible for local therapy, results are available from the open-label, randomised, controlled Phase III HERO trial regarding mortality (overall survival), morbidity (symptoms and health status), health-related quality of life and side effects.
  • In the mortality endpoint category, the available results for the overall survival endpoint show no statistically significant difference between the treatment groups.
  • With regard to morbidity, the available results for the endpoints of symptoms (assessed using the EORTC QLQ-C30 and EORTC QLQ-PR25) and health status (assessed using the EQ-5D VAS) do not reveal any differences between the treatment groups that are relevant for the benefit assessment.
  • With regard to quality of life, the results for the EORTC QLQ-C30 and EORTC QLQ-PR25 also show no statistically significant differences between the treatment groups.
  • Similarly, no statistically significant differences were observed in terms of side effects, with regard to SAE, severe AEs (UE) and therapy discontinuations due to AEs.
  • In summary, no advantages or disadvantages for relugolix can be identified in any of the endpoint categories.
  • In its overall assessment of the available results, the G-BA therefore finds that relugolix offers no additional benefit over leuprorelin.

c) Patients with advanced hormone-sensitive prostate cancer and PSA recurrence or clinical recurrence following primary local therapy

• The additional benefit is not proven.
• For the treatment of adult men with advanced hormone-sensitive prostate cancer and PSA recurrence or clinical recurrence following primary local therapy, the pharmaceutical manufacturer has not provided any data for the assessment of additional benefit. Consequently, additional benefit is not proven.

d1) Patients with metastatic hormone-sensitive prostate cancer (mHSPC) – patients with metastatic hormone-sensitive prostate cancer (mHSPC) who are eligible for combination therapy

• The additional benefit is not proven.
• The pharmaceutical manufacturer has not provided any data for the assessment of additional benefit for the treatment of adult men with metastatic hormone-sensitive prostate cancer who are eligible for combination therapy. Consequently, additional benefit is not proven.

d2) Patients with metastatic hormone-sensitive prostate cancer (mHSPC) – patients with metastatic hormone-sensitive prostate cancer (mHSPC) who are not eligible for combination therapy

• An additional benefit is not proven.
• For the treatment of adult men with metastatic hormone-sensitive prostate cancer who are not eligible for combination therapy, the pharmaceutical manufacturer has not provided any data for the assessment of additional benefit. Consequently, additional benefit is not proven.

Courtesy translation only, please refer to the German original.