Durvalumab (10) – Imfinzi®

• Clinical trials
  • The ADRIATIC double-blind Phase III RCT, which is currently still ongoing, is a three-arm trial. This benefit assessment is based on the durvalumab arm (intervention arm) and the placebo-controlled arm (comparison arm).

Adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiotherapy

• Overall, based on the clear advantage in overall survival, the G-BA concludes that durvalumab offers a considerable additional advantage compared with best supportive care for adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiotherapy, offers considerable additional benefit compared with best supportive care.
• The certainty of the evidence for the established additional benefit is classified as an indication in this assessment.
• mortality
  • In the ADRIATIC trial, overall survival is defined as the time (in months) between randomisation and death from any cause.
  • For the endpoint of overall survival, there is a statistically significant difference in favour of durvalumab compared with best supportive care.
  • The extent of the prolongation in overall survival achieved is regarded as a significant improvement.
• Morbidity – Progression-free survival (failure of curative treatment)
  • Patients in this therapeutic indication were treated with concurrent chemoradiotherapy. In the treatment of non-advanced small-cell lung cancer (LS-SCLC) in adults, concurrent chemoradiotherapy represents a curative treatment approach.
  • If the disease persists or recurs after treatment, this indicates that the curative treatment approach has failed. The failure of a curative treatment approach is generally considered to be of clinical relevance to the patient.
  • No endpoint was specified for the ADRIATIC study to specifically assess the failure of the curative treatment approach. In the dossier, the pharmaceutical manufacturer presents data on progression-free survival (PFS) and discusses its patient relevance in the context of the curative treatment approach.
  • In the G-BA’s view, the PFS endpoint is not suitable in the present situation for adequately reflecting the failure of the curative treatment approach. In the ADRIATIC study, PFS was defined as the time from randomisation to disease progression or death from any cause, whichever occurred first. Accordingly, PFS only captures events in which disease progression occurred during the observation period. Recurrences or events (beyond progression events) that would allow the failure to achieve disease-free status during the follow-up period to be reflected are not part of the operationalisation of PFS.
  • Consequently, it is not possible to make a sufficient assessment as to whether, and in how many patients, the curative treatment approach has failed. The PFS endpoint is not used for the present assessment. The results are presented in the resolution only as supplementary information.
• Health-related quality of life
  • Health-related quality of life was assessed using the EORTC QLQ-C30 questionnaire and operationalised as the time to the first deterioration of ≥ 10 points. For health-related quality of life assessed using the EORTC QLQ-C30 , there was no statistically significant difference between the treatment arms for the endpoints ‘global health status’, ‘physical functioning’, ‘role functioning’, ‘cognitive functioning’, ‘emotional functioning’ and ‘social functioning’ respectively.
  • Overall, therefore, no advantage or disadvantage was identified for the health-related quality of life endpoint category.
• Side effects – Total adverse events (AEs)
  • In the ADRIATIC study, an AE occurred in almost all patients in both the control and intervention arms. The results are presented here for supplementary information only.
• Overall assessment
  • For the assessment of the additional benefit of durvalumab in adults with non-advanced small-cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiotherapy, results on mortality, morbidity, health-related quality of life and side effects from the randomised, multicentre, controlled ADRIATIC study.
  • For the endpoint of overall survival, there is a statistically significant advantage in favour of durvalumab compared with best supportive care. Overall, the results for overall survival are interpreted as a marked improvement.
  • In the morbidity endpoint category, disease symptoms (EORTC QLQ-C30 and -LC13) and health status (EQ-5D VAS) were assessed. Overall, no difference relevant to the benefit assessment was observed here.
  • No advantage or disadvantage was identified with regard to health-related quality of life (EORTC QLQ-C30).
  • In summary, with regard to the side effects of durvalumab, disadvantages are evident in detail for individual specific AEs, although the immune-mediated AEs show low absolute frequencies to the detriment of durvalumab. These disadvantages are not reflected in the overall rates of serious SAEs, severe AEs and treatment discontinuation due to AEs. Overall, no advantage or disadvantage – or any difference relevant to the benefit assessment – was identified for Durvalumab compared with best supportive care in terms of side effects.
  • Overall, based on the clear advantage in overall survival, the G-BA concludes that durvalumab offers a considerable additional advantage over best supportive care for adults with non-advanced small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiotherapy, offers considerable additional benefit compared with best supportive care.

Courtesy translation only, please refer to the German original.