Atezolizumab (4) – Tecentriq®

• Clinical trials
  • The IMpassion 130 trial is a randomised, double-blind, controlled trial comparing atezolizumab plus nab-paclitaxel with nab-paclitaxel alone.

Adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC – triple-negative breast cancer), whose tumours exhibit PD-L1 expression ≥ 1% and who have not previously received chemotherapy for the treatment of metastatic disease

• For atezolizumab in combination with nab-paclitaxel in adult patients for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC – triple-negative breast cancer), whose tumours have PD-L1 expression of ≥ 1% and who have not previously received chemotherapy for the treatment of metastatic disease, there is a hint of a non-quantifiable additional benefit.
• Overall, there is a hint of a non-quantifiable additional benefit.
• Consequently, when considered as a whole, the certainty of the evidence for the established additional benefit is classified as a hint.
• mortality
  • For the endpoint of overall survival, there is a statistically significant difference in favour of atezolizumab + nab-paclitaxel (hazard ratio (HR): 0.71; [95% confidence interval (CI): 0.54; 0.93]; p-value = 0.013).
  • The median overall survival in the treatment arm was 7 months longer than in the control arm (25.0 vs. 18.0 months).
  • The study thus demonstrates a clearly positive effect of atezolizumab + nab-paclitaxel compared with nab-paclitaxel.
• Morbidity – Progression-free survival (PFS)
  • Progression-free survival as assessed by the investigator (INV-PFS) is a co-primary endpoint of the IMpassion130 trial.
  • PFS is defined as the time from randomisation to the date of disease progression, as assessed by the investigator and based on the RECIST v1.1 criteria, or to the date of death from any cause.
  • Treatment with atezolizumab + nab-paclitaxel was associated with a significantly longer progression-free survival compared with nab-paclitaxel (7.5 vs. 5.3 months; HR: 0.63; [95% CI: 0.50; 0.080]; p-value < 0.0001).
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • 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 v1.1 criteria).
• Health-related quality of life
  • Symptoms were assessed in the IMpassion130 study using the functional scales of the disease-specific EORTC QLQ-C30 questionnaire and the breast cancer-specific supplementary module QLQ-BR23.
  • Quality of life was operationalised as the time to the first deterioration (decrease) of 10 points on the respective symptom scale.
  • No statistically significant difference was observed between the treatment arms in any of the functional scales of the EORTC QLQ-C30 (‘overall health status’, ‘role functioning’, ‘physical functioning’, ‘emotional functioning’, ‘cognitive functioning’ and ‘social functioning’) showed a statistically significant difference between the treatment arms.
  • No usable data are available for the ‘sexual satisfaction’ scale.
  • With regard to quality of life, therefore, no advantage or disadvantage of atezolizumab + nab-paclitaxel can be identified.
• Side effects – Adverse events (total AEs)
  • The results for the endpoint ‘total adverse events’ are presented for supplementary purposes only.
  • In the study arm, 100% of patients experienced at least one adverse event, compared with 97.8% in the control arm.
• Overall assessment
  • Data from the IMpass study are available for the assessment of the additional benefit of atezolizumab in combination with nab-paclitaxel for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC – triple-negative breast cancer), whose tumours exhibit PD-L1 expression of ≥ 1% and who have not previously received chemotherapy for the treatment of metastatic disease, data from the IMpassion130 study on mortality, morbidity, quality of life and side effects are available.
  • The comparator, nab-paclitaxel, does not have a marketing authorisation for this therapeutic indication. However, the G-BA concluded that the IMpassion 130 study, with nab-paclitaxel as the comparator, is sufficiently suitable to enable an assessment of the additional benefit of atezolizumab + nab-paclitaxel.
  • In view of the available alternatives, the G-BA takes a critical view of the choice of nab-paclitaxel as the comparator for the IMpassion 130 study and considers the scientific insights gained from this study to be limited.
  • Based on the relevant objections and information contained in the submissions, it must be noted that treatment with nab-paclitaxel only partially reflects the reality of healthcare provision in Germany.
  • Furthermore, there are uncertainties regarding the dosage of 100 mg/m² of nab-paclitaxel administered weekly, which was routinely used in the IMpassion 130 study.
  • With regard to overall survival, the IMpassion 130 study shows a statistically significant, clearly positive effect for atezolizumab + nab-paclitaxel compared with placebo + nab-paclitaxel.
  • With regard to quality of life, there is no advantage or disadvantage for atezolizumab plus nab-paclitaxel.
  • In the category of side effects, disadvantages were observed in terms of discontinuation due to side effects and, more specifically, with regard to certain side effects under atezolizumab plus nab-paclitaxel compared with placebo plus nab-paclitaxel.
  • Overall, the advantage in terms of overall survival is offset by disadvantages in endpoints relating to morbidity and side effects.
  • These disadvantages are considered relevant; however, they do not call into question the positive effect on overall survival.
  • Due to the uncertainties described regarding the comparator nab-paclitaxel, the extent of the additional benefit identified on the basis of the results from the IMPassion 130 study cannot be quantified.

Courtesy translation only, please refer to the German original.