Atezolizumab (11) – Tecentriq®

• Clinical trials
  • For the benefit assessment relating to patient population b), the pharmaceutical manufacturer presents results from the completed, open-label, randomised, controlled Phase III trial IPSOS.

a) Adults with advanced NSCLC with PD-L1 expression ≥ 50% on TC who are considered unsuitable for platinum-based therapy; first-line treatment

• An additional benefit is not proven.
• No data are available to enable an assessment of additional benefit. In its dossier, the pharmaceutical manufacturer does not take patient population a) into account and, accordingly, does not submit any data for the assessment of additional benefit.

b) Adults with advanced NSCLC with PD-L1 expression < 50% on CT, who are considered unsuitable for platinum-based therapy; first-line treatment

• Overall, a minor additional benefit of atezolizumab compared with gemcitabine or vinorelbine is observed.
• The certainty of evidence for the identified additional benefit is classified as an indication.
• mortality
  • In the IPSOS study, overall survival was defined as the time from randomisation to death from any cause.
  • For the endpoint of overall survival, a statistically significant advantage was observed in favour of atezolizumab compared with gemcitabine or vinorelbine; the extent of this advantage is assessed as a relevant improvement, though not exceeding a minor level.
• Morbidity – Progression-free survival (PFS)
  • In the IPSOS study, progression-free survival was defined as the time from randomisation to the first sign of disease progression or to death from any cause, whichever occurred first. The endpoints were assessed by the investigators using the RECIST criteria, version 1.1.
  • No statistically significant difference was observed between the treatment groups for the PFS endpoint.
  • The PFS endpoint in question is a composite endpoint comprising endpoints from the ‘mortality’ and ‘morbidity’ categories. The ‘mortality’ component of the endpoint is already assessed as a standalone endpoint via the ‘overall survival’ endpoint. The ‘disease progression’ component of morbidity is assessed according to RECIST criteria and thus predominantly by means of imaging procedures.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint for patients.
  • This does not affect the overall conclusion regarding the extent of the additional benefit.
• Morbidity – Symptoms (EORTC QLQ-C30 and EORTC QLQ-LC13)
  • Patients’ symptoms are assessed in the IPSOS study using the EORTC QLQ-C30 and the disease-specific supplementary module EORTC QLQ-LC13.
  • Due to the sharply declining and varying response rates, as well as the different timing of data collection for the patient-reported endpoints within the treatment cycles, the results for the patient-reported endpoints cannot be meaningfully interpreted and are therefore not suitable for the benefit assessment.
• Morbidity – Health status (EQ-5D VAS)
  • Patients’ health status is assessed in the IPSOS study using the EQ-5D VAS.
  • Due to the sharply declining and varying response rates, as well as the differing timing of data collection for patient-reported endpoints within the treatment cycles, the results for the patient-reported endpoints cannot be meaningfully interpreted and are therefore not suitable for benefit assessment.
• Health-related quality of life – Health-related quality of life (EORTC QLQ-C30)
  • Patients’ quality of life is assessed in the IPSOS study using the EORTC QLQ-C30.
  • Due to the sharply declining and varying response rates, as well as differing collection times for patient-reported endpoints within the treatment cycles, the results for patient-reported endpoints cannot be meaningfully interpreted and are therefore not suitable for benefit assessment.
• Side effects – Adverse events (AEs)
  • In the IPSOS study, an adverse event occurred in 93% of patients in the intervention arm and in 98.2% of patients in the control arm. The results are presented here for supplementary information only.
• Side effects – SUEs
  • No statistically significant difference was observed between the treatment groups for the SUE endpoint.
• Side effects – severe AEs
  • For the endpoint of severe AEs, there was a statistically significant advantage in favour of atezolizumab compared with gemcitabine and vinorelbine, respectively.
• Side effects – discontinuation due to side effects
  • For the endpoint ‘discontinuation due to adverse events’, there was no statistically significant difference between the treatment groups. However, there was an effect modification by the characteristic of sex. For men, there was a statistically significant advantage in favour of atezolizumab compared with the appropriate comparator therapy. For women, there was no statistically significant difference between the treatment groups. Given that this effect modification is only evident for this single endpoint, the result for the overall population is used for the assessment.
• Overall assessment
  • For the benefit assessment of atezolizumab as monotherapy for the first-line treatment of adults with advanced NSCLC with PD-L1 expression < 50% who are unsuitable for platinum-based therapy, results from the IPSOS study are available for the endpoint categories of mortality, morbidity, health-related quality of life and side effects, compared with monotherapy with gemcitabine or vinorelbine.
  • For the endpoint of overall survival, there is a statistically significant advantage in favour of atezolizumab compared with gemcitabine or vinorelbine; the extent of this advantage is assessed as a relevant improvement, though not exceeding a minor level. With regard to symptoms (assessed using the EORTC QLQ-C30 and EORTC QLQ-LC13), health status (assessed using the EQ-5D VAS) and health-related quality of life (assessed using the EORTC QLQ-C30), the data cannot be meaningfully interpreted due to sharply declining and varying response rates, as well as differing assessment timepoints within the treatment cycles, and are therefore unsuitable for the benefit assessment. In the endpoint category of side effects, there is no statistically significant difference between the study arms with regard to the endpoint of serious AEs. For the endpoint of severe AEs (CTCAE grade ≥ 3), there is a statistically significant advantage for atezolizumab. Furthermore, when examined in detail, atezolizumab demonstrated positive effects compared with monotherapy with gemcitabine or vinorelbine for individual specific AEs. No suitable data are available on immune-mediated AEs or severe immune-mediated AEs.
  • In the overall assessment, a minor additional benefit is identified for atezolizumab compared with monotherapy with gemcitabine or vinorelbine.

Courtesy translation only, please refer to the German original.