Elacestrant (1) – Orserdu®

• Clinical trials
  • In the ongoing, open-label Phase III EMERALD trial, elacestrant is being compared with treatment as prescribed by the doctor, with a choice of fulvestrant, anastrozole, letrozole and exemestane.

a1) Postmenopausal women with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation; who have experienced disease progression following at least one line of endocrine therapy, including a CDK4/6 inhibitor – postmenopausal women who have received one prior line of endocrine therapy

• The conclusion is that there is no additional benefit of elacestrant compared with treatment as clinically indicated for patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation and a history of one prior endocrine therapy is not proven.
• In summary, the G-BA derives a hint of the established additional benefit with regard to the certainty of the findings.
• mortality
  • For patients who have received one prior line of endocrine therapy, there is no statistically significant difference between the treatment arms.
• Morbidity – Progression-free survival (PFS)
  • A statistically significant advantage in favour of elacestrant was observed for PFS compared with treatment as clinically indicated.
  • Irrespective of this, even if the present PFS result were taken into account, the overall conclusion regarding the extent of the additional benefit would remain unchanged.
• Morbidity – Symptoms (EORTC QLQ-C30)
  • For the endpoint of loss of appetite, there is a statistically significant difference in favor of elacestrant compared with treatment as prescribed by the doctor that is associated with a disadvantage.
  • For the endpoint of insomnia, there is no statistically significant difference between the treatment groups. There is an effect modification by the characteristic ‘number of previous endocrine therapy lines’. For patients with one previous endocrine therapy line, there is a statistically significant advantage in the treatment arms for elacestrant.
  • For the endpoints of fatigue, nausea/vomiting, pain, dyspnoea, constipation and diarrhoea, no statistically significant difference was observed between the treatment groups in any case.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint, assessed using the EQ-5D VAS, there was no statistically significant difference between the treatment arms.
• Health-related quality of life
  • For the endpoints of overall health status, physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning, no statistically significant difference was observed between the treatment arms.
  • With regard to health-related quality of life, there is no statistically significant difference between the treatment arms.
• Side effects – total adverse events
  • In the EMERALD study, AEs occurred in almost all participants in both treatment arms.
• Side effects – serious AEs (SAEs), severe AEs and discontinuation due to AEs
  • No statistically significant differences were observed between the treatment groups for the endpoints SAE, severe AEs and discontinuation due to AEs.
• Side effects – Specific adverse events
  • For the endpoints ‘Gastrointestinal disorders’ (SOC, AEs) and ‘Musculoskeletal, connective tissue and bone disorders’ (SOC, severe AEs), a statistically significant difference in favor of elacestrant was observed in the overall population.
• Overall assessment / Conclusion
  • For patients who have previously received one line of endocrine therapy, there is no statistically significant difference between the treatment arms in the endpoint categories of mortality and health-related quality of life.
  • In the categories of morbidity and side effects, there is overall neither an advantage nor a disadvantage to treatment with elacestrant.
  • When the results are considered as a whole, there are neither advantages nor disadvantages across all endpoint categories. For patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation and one prior line of treatment, additional benefit is not proven with elacestrant compared with treatment as clinically indicated.

a2) Postmenopausal women with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation; with disease progression following at least one line of endocrine therapy, including a CDK4/6 inhibitor – postmenopausal women who have received two previous lines of endocrine therapy

• Consequently, the G-BA has determined that elacestrant offers considerable additional benefit for patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation who have received two previous lines of endocrine therapy.
• In summary, the G-BA derives a hint of the established additional benefit in terms of the certainty of the findings.
• Morbidity – Progression-free survival (PFS)
  • For PFS, there is a statistically significant advantage in favour of elacestrant compared with treatment as clinically indicated.
  • Irrespective of this, even if the present PFS result were taken into account, the overall conclusion regarding the extent of the additional benefit would remain unchanged.
• Morbidity – Symptoms (EORTC QLQ-C30)
  • For the endpoint of loss of appetite, there is a statistically significant difference in favor of elacestrant compared with treatment as directed by the doctor that is associated with a disadvantage.
  • For the endpoint of insomnia, there is no statistically significant difference between the treatment groups.
  • For the endpoints of fatigue, nausea/vomiting, pain, dyspnoea, constipation and diarrhoea, no statistically significant difference was observed between the treatment groups in any case.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint, assessed using the EQ-5D VAS, there was no statistically significant difference between the treatment arms.
• Health-related quality of life
  • For the endpoints of overall health status, physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning, there was no statistically significant difference between the treatment arms in any case.
  • With regard to health-related quality of life, there is no statistically significant difference between the treatment arms.
• Side effects – total adverse events
  • In the EMERALD study, AEs occurred in both treatment arms in almost all participants.
• Side effects – serious AEs (SAEs), severe AEs and discontinuation due to AEs
  • No statistically significant differences were observed between the treatment groups for the endpoints SAE, severe AEs and discontinuation due to AEs.
• Side effects – Specific adverse events
  • For the endpoints ‘Gastrointestinal disorders’ (SOC, AEs) and ‘Musculoskeletal, connective tissue and bone disorders’ (SOC, severe AEs), a statistically significant difference to the disadvantage of elacestrant was observed in the overall population.
• Overall assessment / Conclusion
  • For patients who have previously received two lines of endocrine therapy, there is a clear advantage in favour of elacestrant in the mortality endpoint category.
  • In the category of morbidity and side effects, there is neither an overall advantage nor a disadvantage for treatment with elacestrant.
  • No statistically significant difference was observed between the treatment arms in terms of health-related quality of life.
  • Overall, there is an advantage in terms of mortality. In the other endpoint categories, there are neither advantages nor disadvantages overall. The overall assessment indicates a considerable additional benefit of elacestrant compared with treatment as clinically indicated for patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation and a history of two previous lines of treatment.

b) Men with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation; with disease progression following at least one line of endocrine therapy, including a CDK4/6 inhibitor

• The additional benefit is not proven.
• No men were included in the patient population from the EMERALD study that formed the basis for marketing authorisation (ESR1-mut patient population).
• Overall, therefore, no data are available to assess the additional benefit of elacestrant compared with the appropriate comparator therapy. Consequently, the additional benefit is not proven.

Courtesy translation only, please refer to the German original.