Atezolizumab (10) – Tecentriq®

• Clinical trials
  • The pharmaceutical manufacturer has submitted results from the multicentre, open-label, randomised IMpower010 trial for the benefit assessment, in which atezolizumab is compared with best supportive care (BSC).

Adults with completely resected NSCLC at high risk of recurrence following platinum-based chemotherapy, whose tumours exhibit PD-L1 expression in ≥ 50 per cent of tumour cells and who do not have EGFR mutations or ALK-positive NSCLC; adjuvant treatment

• Overall, the positive effect on overall survival is offset by significant disadvantages in terms of side effects.
• The extent of the effect on overall survival indicates a clinically significant improvement compared with watchful waiting; however, given the uncertainties described, this cannot be quantified with certainty.
• Overall, therefore, atezolizumab as monotherapy for the adjuvant treatment of NSCLC following complete resection and platinum-based chemotherapy in adult patients at high risk of recurrence, whose tumours exhibit PD-L1 expression of ≥ 50% and who do not have EGFR-mutated or ALK-positive NSCLC.
• The certainty of evidence for the established additional benefit is classified as ‘hint’.
• Mortality – Overall survival
  • In the IMpower10 trial, 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 watchful waiting.
  • When interpreting the result, it should be borne in mind that, for a significant proportion of patients with recurrence in the control arm of the IMpower010 study, it can be assumed that follow-up treatment was inadequate in relation to the standard of care during the study period.
  • Overall, therefore, significant uncertainties remain regarding the assessment of the extent of the statistically significant difference in favour of atezolizumab compared with watchful waiting, in terms of its transferability to real-world clinical practice.
• Morbidity – Disease-Free Survival (DFS) and Recurrence Rate
  • Disease-free survival (DFS) is defined in the IMpower010 study as the time from randomisation to the first occurrence of any of the following events, whichever occurred first: first documented recurrence of the disease, occurrence of a new primary NSCLC, or death from any cause.
  • The analyses of morbidity from the IMpower010 study submitted by the pharmaceutical manufacturer for the benefit assessment are not usable.
  • Although the longer follow-up period up to the second data cut-off provides data with greater informational content, the pharmaceutical manufacturer has not submitted these either in the dossier or during the commenting procedure.
• Health-related quality of life
  • Data on health-related quality of life were not collected in the IMpower010 study.
• Side effects – Total adverse events (AEs)
  • In the IMpower010 study, AEs occurred in the majority of patients enrolled in both study arms.
• Side effects – serious AEs (SAEs)
  • For the SAE endpoint, a statistically significant disadvantage of atezolizumab compared with watchful waiting was observed.
• Side effects – Severe AEs (CTCAE grade ≥ 3)
  • For the endpoint ‘severe AEs’ (CTCAE grade ≥ 3), there was no statistically significant difference between the treatment arms.
• Side effects – Discontinuation due to AEs
  • For the endpoint ‘discontinuation due to AEs’, a statistically significant disadvantage of atezolizumab compared with watchful waiting was observed.
• Side effects – Immune-mediated SAE and immune-mediated severe AEs
  • No usable data are available for the endpoints immune-mediated SAE and immune-mediated severe AEs.
• Side effects – Other specific side effects
  • For the endpoints fever (PT, AEs), disorders of the skin and subcutaneous tissue (SOC, AE) and infections and parasitic diseases (SOC, SAE), a statistically significant disadvantage of atezolizumab compared with watchful waiting was observed in each case.
• Overall assessment
  • The benefit assessment of atezolizumab as monotherapy for the adjuvant treatment of NSCLC following complete resection and platinum-based chemotherapy in adult patients at high risk of recurrence, whose tumours express PD-L1 expression in ≥ 50% of tumour cells and who do not have EGFR-mutated or ALK-positive NSCLC, is based on results from the IMpower010 study regarding the endpoint categories of mortality, morbidity and side effects compared with watchful waiting.
  • For the endpoint of overall survival, there is a statistically significant advantage in favour of atezolizumab compared with watchful waiting. When interpreting the results, it should be borne in mind that, for a significant proportion of patients with recurrence in the control arm of the IMpower010 study, it can be assumed that follow-up treatment was inadequate in relation to the standard of care during the study period. Overall, therefore, significant uncertainties remain regarding the assessment of the extent of the statistically significant difference in favour of atezolizumab compared with watchful waiting in terms of its transferability to real-world clinical practice.
  • No usable results are available for the patient-relevant endpoints of DFS and recurrences classified as morbidity. Given the curative nature of the treatment approach under consideration, the prevention of recurrence is a key treatment objective.
  • Health-related quality of life endpoints were not assessed in the IMpower010 trial.
  • With regard to side effects, there was no statistically significant difference between the study arms for the endpoint of severe AEs (CTCAE grade ≥ 3). With regard to the endpoints of serious AEs and discontinuation due to AEs, as well as the specific AEs in detail, atezolizumab was associated with negative effects compared with the watch-and-wait approach.
  • Overall, the positive effect on overall survival is offset by relevant disadvantages in terms of side effects. These disadvantages are weighed against the background of the current curative treatment approach and do not, on the whole, call into question the positive effect on overall survival. The extent of the effect on overall survival indicates a clinically significant improvement compared with watchful waiting; however, given the uncertainties described, this cannot be quantified with certainty.

Courtesy translation only, please refer to the German original.