Talazoparib (1) – Talzenna®

• Clinical trials
  • EMBRACA is a multicentre, open-label, randomised controlled trial comparing talazoparib with a chemotherapeutic regimen of the clinician’s choice, using capecitabine, vinorelbine, eribulin or gemcitabine.

Adult patients with HER2-negative, locally advanced or metastatic breast cancer with germline BRCA1/2 mutations; who have previously received therapy with an anthracycline and/or a taxane in a (neo)adjuvant or metastatic setting, or who are unsuitable for these treatments

• For the treatment of adult patients with HER2-negative, locally advanced or metastatic breast cancer with germline BRCA1/2 mutations; following prior treatment with an anthracycline and/or a taxane in a (neo)adjuvant or metastatic setting, or who are unsuitable for these treatments, there is a hint of considerable additional benefit.
• Overall, for these reasons, the certainty of the evidence for the observed additional benefit is classified as a hint.
• mortality
  • For the endpoint of overall survival, no statistically significant difference was observed between the treatment arms.
  • Consequently, no additional benefit is identified for the endpoint of overall survival.
• Morbidity – Progression-free survival (PFS)
  • A statistically significant difference was observed between the treatment groups for progression-free survival, in favour of talazoparib.
• Morbidity – Symptoms
  • For the endpoints of fatigue, pain, insomnia, loss of appetite, side effects of systemic therapy, chest symptoms and arm symptoms, a statistically significant difference was observed in favour of talazoparib compared with chemotherapy.
  • No usable data were available for the endpoint of distress caused by hair loss.
  • For all other endpoints, no statistically significant difference was observed between the study arms.
  • An overall analysis of the results regarding symptoms reveals positive effects of treatment with talazoparib on several symptoms, including both the cancer-specific and breast cancer-specific symptoms assessed, which, taken together, represent a marked improvement in symptoms compared with treatment with capecitabine, vinorelbine or eribulin.
• quality of life
  • For all items of the EORTC QLQ-C30, i.e. the global health status, as well as the functional scales for physical functioning, role functioning, cognitive functioning, emotional functioning and social functioning, and body image on the EORTC QLQ-BR23 questionnaire, a statistically significant advantage was observed for talazoparib.
  • No usable data were available for the endpoint ‘enjoyment of sex’.
  • For the endpoints ‘sexual activity’ and ‘future outlook’, there was no statistically significant difference between the study arms.
  • In view of the positive effects on several, or indeed the majority, of the endpoints assessed for cancer- and breast cancer-specific health-related quality of life – some of which had a substantial extent – an advantage can be identified for treatment with talazoparib compared with treatment with capecitabine, vinorelbine or eribulin in terms of health-related quality of life, the extent of which is assessed overall as a significant improvement.
• Side effects – Total adverse events (AEs)
  • In the EMBRACA trial, an adverse event occurred in 98.5% of patients in the intervention arm, compared with 97.4% of patients in the control arm.
• Side effects – Serious adverse events (SAEs)
  • No statistically significant difference was observed between the study arms with regard to serious adverse events.
• Side effects – Severe AEs (CTCAE Grade 3 or 4)
  • A statistically significant advantage in favour of talazoparib was observed with regard to severe adverse events classified as CTCAE Grade 3 or 4.
• Side effects – Discontinuation due to AEs
  • No statistically significant difference was observed between the study arms for the endpoint of therapy discontinuation due to an AE.
• Side effects – Specific AEs
  • Talazoparib showed statistically significant advantages with regard to the specific AEs of eye diseases, hand-foot syndrome and paraesthesia, as well as specific severe AEs (CTCAE Grade ≥ 3) skin and subcutaneous tissue disorders, neutropenia and diarrhoea.
  • In contrast, talazoparib showed statistically significant disadvantages with regard to the specific severe AEs (CTCAE grade ≥ 3) anaemia and thrombocytopenia.
  • When the endpoints relating to specific AEs are considered as a whole, the positive effects of talazoparib predominate.
  • In the category of side effects, talazoparib therefore shows an overall advantage over capecitabine, vinorelbine or eribulin.
• Overall assessment / Conclusion
  • Results from the open-label, randomised, controlled EMBRACA trial are available for the assessment of the additional benefit of talazoparib compared with capecitabine, vinorelbine or eribulin in terms of mortality (overall survival), morbidity, quality of life and side effects.
  • In the mortality endpoint category, the available results for the overall survival endpoint, based on the study’s overall population, show no statistically significant effect.
  • No additional benefit is identified for the endpoint of overall survival.
  • The results regarding symptoms show positive effects of treatment with talazoparib on several symptoms, including both the cancer-specific and breast cancer-specific symptoms assessed; these are overall assessed as a marked improvement in symptoms compared with treatment with capecitabine, vinorelbine or eribulin.
  • In view of the positive effects on several, or indeed the vast majority, of the assessed endpoints relating to cancer- and breast cancer--specific health-related quality of life – some of which were of a significant extent – an advantage can be identified for treatment with talazoparib, the extent of which is assessed overall as a significant improvement.
  • With regard to side effects, an advantage of talazoparib over capecitabine, vinorelbine or eribulin can be observed for the endpoint of severe adverse events (CTCAE grade 3 or 4).
  • No difference was observed for the endpoints of serious AEs or treatment discontinuation due to AEs.
  • With regard to specific AEs, there are both advantages and disadvantages, but the positive effects outweigh the negative ones.
  • In the category of side effects, talazoparib therefore shows an overall advantage over capecitabine, vinorelbine or eribulin.
  • In its overall assessment, the G-BA concludes, based on the clear advantages in the endpoint categories of morbidity (symptoms) and health-related quality of life – which are of particular relevance in this advanced stage of treatment – as well as on the advantages in the category of side effects, the G-BA identifies a considerable additional benefit for talazoparib compared with capecitabine, vinorelbine or eribulin.

Courtesy translation only, please refer to the German original.