Atezolizumab (1) – Tecentriq®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer cites in the dossier the results of the randomised, open-label, controlled Phase 3 OAK trial, in which atezolizumab was compared with docetaxel.
  • The POPLAR trial is an open-label, randomised, controlled Phase 2 trial (RCT) in which, as in the subsequent Phase 3 OAK trial, atezolizumab was compared with docetaxel.

a) Atezolizumab as monotherapy for the treatment of adult patients with advanced non-small cell lung cancer for whom treatment with docetaxel, pemetrexed, nivolumab or pembrolizumab is indicated following prior chemotherapy

• Indication of a considerable additional benefit.
• Consequently, the certainty of the evidence for the established additional benefit is classified as ‘indication’.
• Mortality – overall survival
  • Treatment with atezolizumab showed a statistically significant prolongation in overall survival compared with treatment with docetaxel (hazard ratio: 0.80 [0.70; 0.92], p-value = 0.001). The median survival time in the atezolizumab group was 13.3 months compared with 9.8 months in the docetaxel group, meaning that atezolizumab achieved a median survival benefit of 3.5 months.
  • Subgroup analyses provide proof of an effect modification by the PD-L1 expression status. In the patient population with high PD-L1 expression on tumour or immune cells (TC 3 or IC 3), there was a statistically significant prolongation of median survival with atezolizumab from 10.8 months (median 20.5 versus 9.7 months, hazard ratio: 0.48 [0.33; 0.69], p-value < 0.001). By contrast, no statistically significant difference was observed in the patient population with lower PD-L1 expression (TC 0/1/2 and IC 0/1/2): 12.3 versus 9.8 months median survival, hazard ratio: 0.87 [0.76; 1.01], p-value = 0.064).
• Morbidity – Progression-free survival (PFS)
  • No statistically significant difference was observed for the endpoint of progression-free survival (PFS): the median PFS was 2.7 months in the intervention arm compared with 3.8 months in the control arm (stratified analysis: hazard ratio: 0.96 [0.85; 1.08], p = 0.4981; unstratified analysis: hazard ratio: 0.95 [0.85; 1.08], p = 0.4532).
  • 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 was assessed via the ‘overall survival’ endpoint as a separate endpoint. The morbidity component was not assessed on the basis of symptoms, 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.
• Health-related quality of life
  • Health-related quality of life was assessed in the study using the functional scales and the scale for measuring overall health status from the disease-specific EORTC QLQ-C30 questionnaire. The assessment is based on an analysis of the ‘time to deterioration in quality of life’ using responder analyses.
  • No statistically significant differences were observed between the treatment groups for any of the scales. Consequently, no advantage or disadvantage can be identified for atezolizumab compared with docetaxel in terms of the treatment’s effect on health-related quality of life.
• Side effects – Total adverse events (AEs)
  • Almost every patient in the study experienced at least one adverse event (AE) at least once, both during treatment with atezolizumab and during treatment with docetaxel. The results for the endpoint ‘Total adverse events’ are therefore presented only as supplementary information.
• Overall assessment
  • Results from the OAK study are available for assessing the additional benefit of atezolizumab as monotherapy for the treatment of adult patients with advanced non-small cell lung cancer for whom treatment with docetaxel, pemetrexed, nivolumab or pembrolizumab following prior chemotherapy, the OAK study provides results on mortality (overall survival), morbidity (symptoms), quality of life and side effects compared with the appropriate comparator therapy (docetaxel).
  • With regard to overall survival, the study results show that treatment with atezolizumab achieves a statistically significant prolongation of survival. The median survival benefit is 3.5 months compared with docetaxel (median 13.3 months versus 9.8 months). The results are interpreted as a marked improvement in overall survival with a considerable extent.
  • Furthermore, the results on patient-reported morbidity demonstrate relevant positive effects of atezolizumab on the disease- and treatment-related symptoms assessed in the study.
  • The data on patient-reported quality of life show that neither an advantage nor a disadvantage can be identified with regard to the effects of atezolizumab compared with docetaxel on health-related quality of life.
  • An overall analysis of the endpoints relating to adverse events reveals a clear advantage of atezolizumab compared with docetaxel, particularly due to a significant reduction in severe adverse events (CTCAE grade ≥ 3) and serious unanticipated events (SAE).
  • The overall assessment identifies a considerable additional benefit for atezolizumab compared with docetaxel in the treatment of adult patients with advanced non-small cell lung cancer for whom treatment with docetaxel, pemetrexed, nivolumab or pembrolizumab following prior chemotherapy.

b) Atezolizumab as monotherapy for the treatment of adult patients with advanced non-small cell lung cancer for whom treatment with docetaxel, pemetrexed, nivolumab and pembrolizumab following prior chemotherapy is not indicated

• The additional benefit is not proven.
• No data are available for the assessment of the additional benefit of atezolizumab in adult patients with advanced non-small cell lung cancer following prior chemotherapy, for whom treatment with docetaxel, pemetrexed, nivolumab or pembrolizumab is not indicated.

Courtesy translation only, please refer to the German original.