Atezolizumab (5) – Tecentriq®

• Clinical trials
  • Study E4599 is a randomised, controlled, open-label, parallel-group study comparing paclitaxel + carboplatin with bevacizumab + paclitaxel + carboplatin.

a) Adults with metastatic non-small cell lung cancer with non-squamous histology and a Tumour Proportion Score [TPS] of ≥ 50% (PD-L1 expression) and without EGFR mutations or ALK translocations; First-line treatment

• For the treatment of adults with metastatic non-small cell lung cancer with non-squamous histology and a Tumour Proportion Score [TPS] of ≥ 50 % (PD-L1 expression) and without EGFR mutations or ALK translocations; first-line treatment, additional benefit is not proven.
• The pharmaceutical manufacturer has not submitted any data for the assessment of additional benefit, as it was unable to identify any suitable studies for comparison with the appropriate comparator therapy.
• An assessment of additional benefit is not possible on the basis of this data. Consequently, additional benefit is not proven.

b) Adults with metastatic non-small cell lung cancer with non-squamous histology; and a Tumour Proportion Score [TPS] of < 50 % (PD-L1 expression); First-line treatment; or EGFR-mutated or ALK-positive NSCLC, regardless of the Tumour Proportion Score [TPS], following prior treatment with an appropriate targeted therapy

• For the treatment of adults with metastatic non-small cell lung cancer with non-squamous histology; and a Tumour Proportion Score [TPS] of < 50 % (PD-L1 expression); first-line treatment; or EGFR-mutated or ALK-positive NSCLC, regardless of the tumour proportion score [TPS], following prior treatment with an appropriate targeted therapy, an additional benefit is not proven.
• The adjusted indirect comparison presented is not usable.
• On the basis of this data, it is not possible to assess any additional benefit of atezolizumab + bevacizumab + paclitaxel + carboplatin compared with the appropriate comparator therapy. Therefore, additional benefit is not proven.
• In the IMpower150 study, PD-L1 expression in tumour tissue was determined by the proportion of PD-L1-positive tumour cells (TC) and PD-L1-positive immune cells (IC).
• It is viewed critically that the pharmaceutical manufacturer has not provided a comprehensible and sound justification as to the extent to which, in particular, PD-L1 expression in IC3 actually corresponds to a TPS ≥ 50%.
• There is a period of approximately 12 years between the respective final data collection points of the two studies.
• During this period, there were significant changes and innovations in the management of NSCLC, which are reflected, amongst other things, in differences in first-line and subsequent therapies.
• One inclusion criterion for the IMpower150 study was that patients with an EGFR mutation or ALK translocation were only enrolled after failure of a previous corresponding targeted therapy.
• These targeted prior therapies were not available to patients in the E4599 study.
• Only patients with non-squamous NSCLC were included in the IMpower150 study, whereas this was not an inclusion criterion for the E4599 study.
• Furthermore, the E4599 study lacks data on other characteristics such as smoking status, time since diagnosis of the disease, tumour size at the start of the study, and concomitant treatments.

Courtesy translation only, please refer to the German original.