Atezolizumab (7) – Tecentriq®

• Clinical trials
  • The pharmaceutical manufacturer has submitted data from the randomised, double-blind, placebo-controlled Phase III trial IMpower133, which is currently still ongoing, for the benefit assessment.

Adult patients with advanced small-cell lung cancer (ES-SCLC); first-line treatment

• The overall assessment concludes that, whilst the positive effect on overall survival is not supported by further positive effects on patient-relevant endpoints, the disadvantages associated with side effects do not entirely outweigh this positive effect either.
• Consequently, in terms of the certainty of the findings, only a hint of additional benefit can be inferred.
• mortality
  • Overall survival is defined in the IMpower133 study as the time from randomisation to death from any cause.
  • The meta-analysis of the event time analyses for both study cohorts reveals a statistically significant difference in favour of atezolizumab in combination with carboplatin and etoposide compared with carboplatin in combination with etoposide (HR: 0.79 [95% CI: 0.65; 0.97], p = 0.026).
  • In the mortality endpoint category, based on the results of the IMpower133 study, there is a minor prolongation of overall survival and thus a minor additional benefit.
• Morbidity – Progression-free survival (PFS)
  • PFS is a co-primary endpoint of the IMpower133 trial and is defined as the time from randomisation to the first occurrence of disease progression according to RECIST or death from any cause.
  • At the time of the first data cut-off, PFS was statistically significantly prolonged by a median of 0.9 months in the intervention arm of the global cohort compared with the control arm (median 5.2 vs. 4.3 months; (HR: 0.77 [0.62; 0.96]; p < 0.017).
  • In the Chinese cohort, no statistically significant difference was observed between the treatment groups at the time of the first data cut-off. A meta-analytic summary of the cohorts is not available.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity. In this study, the mortality component of the endpoint is assessed as a standalone endpoint via the overall survival endpoint. The morbidity component is not assessed on a symptom-by-symptom basis, but exclusively by means of imaging procedures (radiologically determined disease progression according to the RECIST criteria). Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint to patients. This does not affect the overall conclusion regarding the extent of the additional benefit.
• Morbidity – Symptoms
  • In the IMpower133 study, patients’ symptoms are assessed using the symptom scales of the EORTC-QLQ-C30 and EORTC-QLQ-LC13 questionnaires.
  • In the meta-analytic summary of the responder analyses for the time to a deterioration of at least 10 points from baseline, there is no statistically significant difference between the treatment groups on any symptom scale.
  • Overall, no additional benefit was observed with treatment using atezolizumab in combination with carboplatin and etoposide in terms of symptoms and health status.
• Health-related quality of life
  • Health-related quality of life is reported by patients in the IMpower133 study and assessed using the functional scales of the EORTC-QLQ-C30 questionnaire.
  • In the meta-analytic summary of the responder analyses for the time to a deterioration of at least 10 points from baseline, there is no statistically significant difference between the treatment groups on any functional scale.
• Side effects – Total adverse events (AEs)
  • In the IMpower133 study, almost all patients in the intervention and control arms of both cohorts experienced an adverse event. The results for the endpoint ‘total adverse events’ are presented here only as supplementary information.
• Overall assessment
  • Results from the Impower133 study on overall survival, morbidity, health-related quality of life and adverse events are available for the benefit assessment of atezolizumab in combination with carboplatin and etoposide as first-line treatment for adult patients with advanced small cell lung cancer (ES-SCLC), results from the Impower133 study on overall survival, morbidity, health-related quality of life and side effects are available. Where possible, the assessment is based on the meta-analytical summary of the results from the two cohorts investigated in this study (global and Chinese cohorts).
  • In the endpoint category of mortality, there is a statistically significant difference between the treatment arms. Atezolizumab in combination with carboplatin and etoposide results in a minor prolongation of overall survival compared with carboplatin in combination with etoposide, which is classified as a minor additional benefit.
  • With regard to morbidity, as assessed using the EORTC-QLQ-C30 and EORTC-QLQ-LC13 questionnaires and the visual analogue scale of the EQ-5D, no differences were observed. In particular, no advantages were observed with regard to the effects on disease-specific symptoms. Symptoms in advanced SCLC are usually pronounced and distressing for patients. Effects on symptoms are therefore significant for patients.
  • Nor were there any differences between the treatment arms in terms of health-related quality of life, as measured by the functional scales of the EORTC-QLQ-C30.
  • On the other hand, there are disadvantages in terms of treatment discontinuations due to AEs; furthermore, a detailed analysis of specific AEs reveals an increase in immune-mediated AEs, immune-mediated serious AEs and immune-mediated severe AEs (CTCAE grades 3 and 4).
  • In the overall assessment, it is noted that, whilst the positive effect on overall survival is not supported by further positive effects on patient-relevant endpoints, the disadvantages associated with side effects do not entirely outweigh this positive effect. In a balancing assessment, the G-BA has therefore concluded in this case that the advantage in terms of overall survival outweighs the disadvantages. Consequently, a minor additional benefit is identified for atezolizumab in combination with carboplatin and etoposide as first-line treatment for adult patients with advanced small-cell lung cancer, compared with carboplatin in combination with etoposide.

Courtesy translation only, please refer to the German original.