Talazoparib (2) – Talzenna®

• Clinical trials
  • Part 2 of the TALAPRO-2 study is a randomised, controlled, double-blind Phase III trial; in Part 2, which is relevant to the benefit assessment, talazoparib in combination with enzalutamide is compared with enzalutamide alone.

a1) Adults with metastatic castration-resistant prostate cancer (mCRPC) for whom chemotherapy is not clinically indicated and who have not previously received treatment for mCRPC – adults without HRR deficiency

• Hint of less benefit.
• Particularly due to the uncertainty regarding the extent to which chemotherapy was clinically contraindicated for all patients in the TALAPRO-2 trial, there is a ‘hint’ of additional benefit with regard to the validity of the evidence.
• mortality
  • The meta-analysis shows no statistically significant difference between the treatment groups.
  • When considering the results in adults without HRR deficiency, there is also no statistically significant difference between the treatment groups.
• Morbidity – Symptoms (EORTC QLQ-C30 and EORTC QLQ-PR25)
  • In adults with and without HRR deficiency, talazoparib is associated with a disadvantage on the ‘nausea and vomiting’ symptom scale.
  • Statistically significant differences to the detriment of talazoparib in combination with enzalutamide are also evident in the ‘fatigue’, ‘dyspnoea’ and ‘loss of appetite’ symptom scales.
• Morbidity – Symptomatic bone fracture and spinal cord compression
  • There is no statistically significant difference between the treatment arms.
• Health-related quality of life (EORTC QLQ-C30 and EORTC QLQ-PR25)
  • In adults without HRR deficiency, statistically significant disadvantages were observed in the functional scales ‘overall health status’, ‘physical functioning’ and ‘role functioning’.
• Side effects
  • In the meta-analysis, statistically significant disadvantages compared to talazoparib in combination with enzalutamide were observed for adverse events (AEs), severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs.
  • In detail, the meta-analysis reveals statistically significant differences in favour of enzalutamide in combination with talazoparib that are disadvantageous for the specific AEs ‘infections and parasitic diseases’, ‘anaemia’ and ‘investigations’.
  • In patients without HRR deficiency, there was also a statistically significant disadvantage for the specific AE ‘dizziness’.
• Overall assessment
  • Taking the results as a whole, on the one hand, no additional benefit for talazoparib in combination with enzalutamide compared with enzalutamide alone can be identified for any endpoint category based on the results of the TALAPRO-2 study.
  • On the other hand, disadvantages are evident in terms of morbidity, health-related quality of life and side effects, and thus there is a clear overall disadvantage to treatment with talazoparib in combination with enzalutamide.
  • Given the relevant disadvantages identified, coupled with the absence of any positive effects, the available data do not support any additional benefit of talazoparib in combination with enzalutamide compared with enzalutamide monotherapy in the treatment of adults with untreated metastatic castration-resistant prostatecarcinoma without HRR deficiency.
  • Rather, the G-BA concurs with the IQWiG’s assessment findings from dossier evaluation A24-22 of 13 May 2024 and, in accordance with Section 5(7)( 6 of the AM-NutzenV, that talazoparib in combination with enzalutamide offers less benefit than enzalutamide monotherapy in the treatment of adults with previously untreated metastatic castration-resistant prostate cancer without HRR deficiency.

a2) Adults with metastatic castration-resistant prostate cancer (mCRPC) for whom chemotherapy is not clinically indicated and who have not received prior treatment for mCRPC – adults with HRR deficiency

• The additional benefit is not proven.
• mortality
  • The meta-analysis shows no statistically significant difference in the endpoint of overall survival between the treatment groups.
  • For adults with HRR deficiency, whilst the results show a statistically significant difference between the treatment groups in favour of talazoparib, there is no statistically significant interaction test when compared with the patient population of adults without HRR deficiency.
  • Against this background, no separate assessment of additional benefit is carried out.
• Morbidity – Symptoms (EORTC QLQ-C30 and EORTC QLQ-PR25)
  • In adults with HRR deficiency, advantages are observed on the ‘pain’ and ‘urinary tract symptoms’ symptom scales.
• Morbidity – Symptomatic bone fracture and spinal cord compression
  • Neither positive nor negative effects are observed.
• Health-related quality of life (EORTC QLQ-C30 and EORTC QLQ-PR25)
  • In adults with HRR deficiency, a statistically significant advantage is observed on the ‘physical functioning’ scale.
• Side effects
  • In the meta-analysis, statistically significant disadvantages compared to talazoparib in combination with enzalutamide were observed for adverse events (AEs), severe adverse events (CTCAE grade ≥ 3) and therapy discontinuations due to AEs.
  • In detail, the meta-analysis revealed statistically significant differences in favour of enzalutamide in combination with talazoparib for the specific adverse events ‘infections and parasitic diseases’, ‘anaemia’ and ‘investigations’.
• Overall assessment
  • Taken as a whole, therefore, the only disadvantages relate to side effects.
  • In its decision-making process, the G-BA concludes that, for talazoparib in combination with enzalutamide for the treatment of adults with untreated metastatic castration-resistant prostate cancer with HRRdeficiency does not provide any additional benefit compared with monotherapy with enzalutamide.

b) Adults with metastatic castration-resistant prostate cancer (mCRPC) for whom chemotherapy is not clinically indicated and who have already received prior treatment for mCRPC

• The additional benefit is not proven.
• For the treatment of adult men with metastatic castration-resistant prostate cancer in whom chemotherapy is not clinically indicated and who have already received prior treatment for mCRPC, the pharmaceutical manufacturer has not submitted any data for the assessment of additional benefit.

Courtesy translation only, please refer to the German original.