Atezolizumab (12) – 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

• As a result, atezolizumab monotherapy has been found to offer considerable added benefit over watchful waiting 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 in ≥ 50 per cent of tumour cells (tumour cells, TC) and who do not have EGFR-mutated or ALK-positive NSCLC;
• The certainty of evidence for the observed 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.
  • Based on the data for the relevant patient population regarding the follow-up treatments administered after discontinuation of study medication, it is particularly striking that, in the comparator arm, relatively few patients with recurrence received antineoplastic follow-up therapy and that the proportion receiving checkpointinhibitors as follow-up therapy was minor.
  • Overall, for a significant proportion of patients with recurrence in the control arm of the IMpower010 trial, it can be assumed that follow-up therapy was inadequate in relation to the standard of care during the trial period. Given the magnitude of the effect, the advantage of atezolizumab in terms of the overall survival endpoint is not in doubt; however, its extent is non-quantifiable.
• morbidity
  • Recurrences
  • These endpoints are represented by the recurrence rate and disease-free survival, and include the events of local recurrence, regional recurrence, distant recurrence, new primary NSCLC and death (without prior recurrence).
  • The recurrence rate is defined as the proportion of patients who, following complete tumour resection, experience a recurrence, develop a new primary NSCLC or die by the current data cut-off date. The first qualifying event is considered the event.
  • Disease-free survival is defined as the time from randomisation to the occurrence of a recurrence, a new primary NSCLC or death, whichever occurs first.
  • For both endpoints (recurrence rates and disease-free survival), there is a statistically significant advantage in favour of atezolizumab compared with watchful waiting, whose extent is assessed as a marked improvement. The prevention of recurrence represents an essential therapeutic goal in the present curative treatment setting. The (high-)risk period is considered to be covered by the current observation period.
• 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. The results were presented for supplementary information only.
  • Serious AEs (SAEs)
  • For the SAE endpoint, a statistically significant disadvantage of atezolizumab compared with watchful waiting was observed.
  • Severe AEs (CTCAE grade ≥ 3)
  • For the endpoint of severe AEs (CTCAE grade ≥ 3), there was no statistically significant difference between the treatment arms.
  • Therapy discontinuation due to AEs
  • For the endpoint ‘therapy discontinuation due to AEs’, a statistically significant disadvantage of atezolizumab compared with watchful waiting was observed.
  • Specific AEs
  • Immune-mediated SAE and immune-mediated severe AE
  • No usable data are available for the endpoints ‘immune-mediated SAE’ and ‘immune-mediated severe AE’.
  • Other specific AEs
  • For the endpoints fever (PT, AE), 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 is observed in each case.
  • In summary, within the endpoint category of side effects, a disadvantage can be identified for treatment with atezolizumab due to negative effects in SAE and therapy discontinuation due to AEs. With regard to specific adverse events, there are detailed disadvantages for atezolizumab.
• 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 exhibit 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 trial 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. Given the magnitude of the effect, the advantage of atezolizumab in terms of the overall survival endpoint is not called into question; however, the extent of this advantage is non-quantifiable.
  • With regard to the results on recurrence, presented as recurrence rate and disease-free survival, an advantage of atezolizumab compared with watchful waiting is observed, the extent of which is assessed as a significant improvement. The prevention of recurrence represents an essential therapeutic goal in the present curative treatment setting.
  • On balance, the advantage in overall survival and the significant advantage in the recurrence endpoint are offset by disadvantages relating to side effects. These disadvantages are weighed against the background of the current curative treatment approach and do not call into question the extent of the improvement in the overall assessment.

Courtesy translation only, please refer to the German original.