Dostarlimab (2) – Jemperli®

• Clinical trials
  • The RUBY trial is a two-part, randomised, controlled, double-blind Phase III trial; in Part 1, which is relevant to the benefit assessment, dostarlimab in combination with carboplatin and paclitaxel is compared with carboplatin in combination with paclitaxel.

a1) Adult female patients with primary advanced endometrial cancer (stage III or IV) or with recurrent endometrial cancer with high-frequency microsatellite instability (MSI-H) or with mismatch repair deficiency (dMMR), who are being treated – patients with primary advanced disease

• Consequently, the G-BA concludes that, for dostarlimab in combination with carboplatin and paclitaxel compared with carboplatin and paclitaxel for patients with primary advanced disease (FIGO stage III and FIGO stage IV), that the additional benefit is not proven.
• mortality
  • For patients in FIGO stages III and IV, the subgroup analyses show no difference between the treatment arms in either case; consequently, no advantage can be inferred from a summary interpretation of the data.
• Morbidity – Symptoms (tingling/numbness)
  • In the morbidity endpoint category, for patients with primary advanced disease at FIGO Stage IV, the endpoint ‘time to first worsening’ on the ‘tingling/numbness’ symptom scale of the EORTC QLQ-EN24. A statistically significant advantage for Dostarlimab in combination with Carboplatin and Pacl
  • For patients with primary advanced disease at FIGO stage III, the subgroup analysis shows no difference between the treatment arms.
  • Overall, a summary interpretation of the data reveals no differences relevant to the benefit assessment.
• Morbidity – Health status (EQ-5D VAS)
  • For the endpoint ‘time to first deterioration in health status’, assessed using the EQ-5D VAS, there was no statistically significant difference between the treatment arms in the overall population.
• Health-related quality of life
  • When the results on health-related quality of life are considered as a whole, there is a moderate advantage in favour of dostarlimab in combination with carboplatin and paclitaxel, both in patients with primarily advanced disease and in those with recurrent disease.
  • For the endpoint ‘time to first deterioration in health-related quality of life’, assessed using the EORTC QLQ-C30 and EORTC QLQ-EN24, a statistically significant advantage in favour of dostarlimab in combination with carboplatin and paclitaxel compared with carboplatin in combination with paclitaxel was observed in the ‘role functioning’ and ‘social functioning’ subscales.
• Side effects – severe adverse events (SAEs)
  • For the endpoints SAE, severe AEs and discontinuation due to AEs, there were no statistically significant differences between the treatment arms in the overall population.
  • However, in patients with primary advanced disease at FIGO stage III, a statistically significant disadvantage was observed for dostarlimab in combination with carboplatin and paclitaxel for the endpoint of severe AEs.
  • For patients with FIGO stage IV disease, the subgroup analysis showed no difference between the treatment arms.
  • In the summary interpretation of the data, no disadvantage can be inferred for patients with primary advanced disease.
• Overall assessment
  • Overall, there is only a moderate advantage in health-related quality of life, which is offset by a disadvantage in terms of severe AEs, given the limited statistical power of the subgroup analysis for this endpoint.
  • Taking into account the results for all other patient-relevant endpoints, no overall advantage or disadvantage can be identified for dostarlimab in combination with carboplatin and paclitaxel.

a2) Adult female patients with primary advanced endometrial cancer (stage III or IV) or with recurrence of endometrial cancer with high-frequency microsatellite instability (MSI-H) or with mismatch repair deficiency (dMMR), who are being treated – patients with recurrent disease

• Consequently, the G-BA has determined that dostarlimab in combination with carboplatin and paclitaxel offers a major additional benefit compared with carboplatin and paclitaxel alone.
• The certainty of the evidence for the established additional benefit is classified as an indication.
• mortality
  • For the endpoint of overall survival, there is a statistically significant advantage in favour of dostarlimab in combination with carboplatin and paclitaxel.
  • The extent of the prolongation in overall survival achieved is assessed as a very marked improvement.
• Health-related quality of life
  • In the health-related quality of life endpoint category, there are moderate advantages of dostarlimab in combination with carboplatin compared with carboplatin in combination with paclitaxel.
  • For the endpoint ‘time to first deterioration in health-related quality of life’, assessed using the EORTC QLQ-C30 and EORTC QLQ-EN24, a statistically significant advantage in favour of dostarlimab in combination with carboplatin and paclitaxel, compared with carboplatin in combination with paclitaxel, was observed in the ‘role functioning’ and ‘social functioning’ subscales.
• Side effects
  • For the endpoint category of side effects, the overall analysis reveals neither an advantage nor a disadvantage for dostarlimab in combination with carboplatin and paclitaxel compared with carboplatin in combination with paclitaxel.
• Overall assessment
  • Overall, a major additional benefit of dostarlimab in combination with carboplatin and paclitaxel compared with carboplatin in combination with paclitaxel is identified.

Courtesy translation only, please refer to the German original.