Durvalumab (11) – Imfinzi®

• Clinical trials
  • The pharmaceutical manufacturer presents the results from the ongoing, open-label, randomised, controlled Phase III NIAGARA trial comparing durvalumab in combination with gemcitabine + cisplatin (neoadjuvant) and subsequent durvalumab monotherapy (adjuvant) following radical cystectomy, compared with gemcitabine plus cisplatin (neoadjuvant) followed by watchful waiting after radical cystectomy.

Adults with resectable muscle-invasive bladder cancer (MIBC) who are suitable for platinum-based chemotherapy; neoadjuvant and adjuvant therapy

• The findings indicate that durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant), offers a minor additional benefit compared with gemcitabine in combination with cisplatin followed by watchful waiting.
• The certainty of the evidence for the observed additional benefit is classified as an indication.
• mortality
  • In the NIAGARA trial, overall survival is defined as the time from randomisation to death from any cause.
  • For the endpoint of overall survival, a statistically significant difference was observed between the treatment groups in favour of durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant).
  • The extent of the prolongation in overall survival achieved is assessed as a relevant improvement.
• Morbidity – Failure of the curative treatment approach (event rate and event-free survival)
  • In the NIAGARA study, failure of the curative treatment approach was not directly assessed as an endpoint. In the pharmaceutical manufacturer’s dossier, for the purposes of this assessment, the events recorded as part of the primary endpoint of the NIAGARA study – the composite endpoint of event-free survival – were considered, by way of approximation, as the operationalisation of the endpoint.
  • Both the event rate and event-free survival show a statistically significant advantage for durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant).
  • When both endpoints are considered together, a minor overall advantage is observed for Durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by Durvalumab (adjuvant), in terms of preventing failure of the curative treatment approach.
• Morbidity – Symptoms (assessed using the EORTC QLQ-C30 and PGIS)
  • For the endpoints assessed using the EORTC QLQ-C30 – fatigue, nausea and vomiting, pain, dyspnoea, insomnia, loss of appetite, constipation and diarrhoea – no statistically significant difference was observed between the treatment groups in any case.
  • Furthermore, no statistically significant difference was observed between the treatment groups for the symptoms assessed using the PGIS.
• Morbidity – Health status (assessed using the EQ-5D VAS and PGIC)
  • For health status assessed using the EQ-5D VAS, there was no statistically significant difference between the treatment groups in the overall population.
  • For health status as assessed by the PGIC, a statistically significant advantage was observed in favour of durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant).
• quality of life
  • For the endpoints of role functioning and social functioning, there was no statistically significant difference between the treatment groups in the overall population.
  • For the endpoints of global health status, physical functioning, emotional functioning and cognitive functioning, no statistically significant difference was observed between the treatment groups in any case.
• Side effects – Serious adverse events (SAE) and severe adverse events (CTCAE grade ≥ 3)
  • For the endpoints SAE and severe AEs, no statistically significant difference was observed between the treatment arms in either case.
• Side effects – Immune-mediated severe adverse events
  • For the endpoints of immune-mediated SUEs and immune-mediated severe AEs, a statistically significant difference was observed in each case to the disadvantage of durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant).
• Side effects – Anaemia (preferred term (PT), serious adverse events (SUEs))
  • For the endpoint anaemia (PT, SUEs), there was a statistically significant advantage in favour of durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant).
• Overall assessment
  • For the endpoint of overall survival, there is a statistically significant difference between the treatment groups in favour of durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant). The extent of the prolongation in overall survival achieved is considered a relevant improvement.
  • With regard to failure of the curative treatment approach, as represented by the event rate and event-free survival (EFS), an advantage was observed for durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant), the extent of which is assessed as a minor improvement.
  • Furthermore, an advantage is observed in terms of health status (assessed using the PGIC).
  • Based on the results for symptoms (assessed using the EORTC QLQ-C30 and PGIS), health status (assessed using the EQ-5D VAS) and health-related quality of life (assessed using the EORTC QLQ-C30), neither an advantage nor a disadvantage can be inferred for durvalumab in combination with gemcitabine and cisplatin (neoadjuvant), followed by durvalumab (adjuvant).

Courtesy translation only, please refer to the German original.