Atezolizumab (6) – Tecentriq®

• Clinical trials
  • In the IMpower130 trial, atezolizumab + nab-paclitaxel + carboplatin was compared with nab-paclitaxel + carboplatin.

a) Adult patients 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- or ALK-positive tumour mutations; First-line treatment

• The additional benefit is not proven.
• For first-line treatment of patients with a TPS of ≥ 50 %, non-squamous histology and no EGFR- or ALK-positive tumour mutations, no data were submitted to assess the additional benefit of atezolizumab in combination with nab-paclitaxel and carboplatin compared with the appropriate comparator therapy.

b) Adult patients 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- or ALK-positive tumour mutations; First-line treatment

• An additional benefit is not proven.
• In summary, for first-line treatment of metastatic non-squamous NSCLC without EGFR- or ALK-positive tumour mutations in patients with PD-L1 expression of < 50 % (TPS), an additional benefit of atezolizumab in combination with nab-paclitaxel and carboplatin compared with nab-paclitaxel and carboplatin alone has not been demonstrated when considering the overall results regarding mortality, morbidity, quality of life and side effects, additional benefit is not proven for atezolizumab in combination with nab-paclitaxel and carboplatin compared with nab-paclitaxel and carboplatin.
• mortality
  • Overall survival is defined as the time from randomisation to death from any cause.
  • In the IMpower130 trial, the median survival time at the time of the second data cut-off on 4 September 2018 for the NEoM population relevant for evaluation was 13.1 months in the control arm and 18.2 months in the intervention arm (hazard ratio (HR): 0.83; 95% CI [0.66; 1.03], p-value = 0.096). Overall, the difference is not statistically significant.
  • An additional benefit of atezolizumab in combination with nab-paclitaxel and carboplatin for the endpoint of mortality is not proven.
• Morbidity – Progression-free survival (PFS)
  • For progression-free survival (PFS), a statistically significant difference was observed in favour of atezolizumab in combination with nab-paclitaxel and carboplatin (HR = 0.79; 95% CI [0.64; 0.96], p-value = 0.0204). The median PFS was 6.5 months in patients in the control arm and 7.1 months in patients in the intervention arm.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint.
  • Accordingly, the prolonged PFS was not associated with any advantage in terms of morbidity or quality of life.
• Morbidity – Symptoms
  • To assess symptoms, the IMpower130 study used the symptom scales from the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires.
  • Neither questionnaire revealed any statistically significant differences between the study arms.
  • An additional benefit of atezolizumab in combination with nab-paclitaxel and carboplatin for the endpoint of symptoms is therefore not proven.
• Morbidity – Health status
  • In the IMpower130 trial, health status was assessed using the visual analogue scale (VAS) of the EQ-5D questionnaire.
  • The responder analyses, based on a MID of 10 points, show no statistically significant differences between the study arms.
  • The additional benefit of atezolizumab in combination with nab-paclitaxel and carboplatin for the health status endpoint is not proven.
• Health-related quality of life
  • To assess health-related quality of life, the functional scales of the EORTC QLQ-C30 questionnaire were used in the IMpower130 study.
  • Subgroup analyses revealed an effect modification for the characteristic of liver metastases at the start of the study.
  • Furthermore, the subgroup analyses for the endpoint ‘social functioning’ (interaction: p-value = 0.003) revealed an effect modification for the characteristic ‘smoking status’.
  • Thus, taking the NEoM population into account, there is no additional benefit of atezolizumab in combination with nab-paclitaxel and carboplatin for the quality of life endpoint category.
• Side effects – severe adverse events (CTCAE Grade 3–4)
  • For the endpoint of severe AEs (CTCAE Grade 3–4), there is a statistically significant difference to the detriment of atezolizumab in combination with nab-paclitaxel and carboplatin compared with nab-paclitaxel and carboplatin (HR: 1.24; 95% CI [1.03; 1.49]; p = 0.026).
• Side effects – Specific adverse events (severe AEs, CTCAE Grade 3–4)
  • In this regard, for disorders of the blood and lymphatic system (SOC) and investigations (SOC), syncope (PT) and dyspnoea (PT), there was a statistically significant difference to the detriment of atezolizumab in combination with platinum-based chemotherapy compared with platinum-based chemotherapy alone.
• Side effects – Discontinuation due to adverse events (AEs)
  • For the endpoint of discontinuation due to AEs, there was no statistically significant difference between the treatment arms.
• Overall assessment
  • An additional benefit is not proven for treatment with atezolizumab in combination with nab-paclitaxel and carboplatin in terms of overall survival, as no statistically significant difference was observed between the treatment arms.
  • With regard to health status, as measured by the EQ-5D VAS, and symptoms, as measured by the EORTC QLQ-C30 and EORTC QLQ-LC13, there are no statistically significant differences between the treatment arms.
  • Similarly, for the quality of life endpoint category based on the NEoM population, as assessed using the functional scales of the EORTC QLQ-C30, there were no statistically significant differences between the treatment arms.
  • With regard to adverse events, no meaningful conclusions can be drawn for the endpoints of serious adverse events (SAEs) or for specific adverse events of immune-mediated side effects.
  • For severe AEs (CTCAE Grade 3–4) and a selection of specific severe AEs (CTCAE Grade 3–4), a disadvantage was observed for atezolizumab in combination with nab-paclitaxel and carboplatin.
  • Overall, there are no statistically significant differences for the endpoint categories of overall survival, morbidity and quality of life.
  • The disadvantages for atezolizumab in combination with nab-paclitaxel and carboplatin in terms of severe AEs (CTCAE Grade 3–4) are considered to be clinically significant for patients.
  • However, taking into account the rate of therapy discontinuation – which does not differ statistically significantly between the treatment groups – the disadvantages in terms of side effects are not, on the whole, considered serious enough to justify a finding of less benefit in the overall assessment.

Courtesy translation only, please refer to the German original.