Evaluation of atezolizumab immunogenicity: Efficacy and safety (Part 2)
Solange Peters1, Peter R Galle2, Coen A Bernaards3
1Oncology Department - CHUV, Lausanne University, Lausanne, Switzerland.
Abstract:
Antibody therapeutics can be associated with unwanted immune responses resulting in the development of anti-drug antibodies (ADA). Optimal methods to evaluate the potential effects of ADA on clinical outcomes in oncology are not well established. In this study, we assessed efficacy and safety, based on ADA status, in patients from over 10 clinical trials that evaluated the immune checkpoint inhibitor atezolizumab as a single agent or as combination therapy for several types of advanced cancers. ADA can only be observed post randomization, and imbalances in baseline prognostic factors can confound the interpretation of ADA impact. We applied methodology to account for the confounding effects of baseline clinical characteristics and survivorship bias on efficacy. Adjusted meta-analyses revealed that despite numerical differences in overall survival and progression-free survival between ADA-positive and ADA-negative patients from some studies, ADA-positive patients from studies with an overall treatment effect derived benefit from atezolizumab, compared with their adjusted controls. Based on large, pooled populations from atezolizumab monotherapy or combination studies, unadjusted descriptive analyses did not identify a clear relationship between ADA status and frequency or severity of adverse events. Data also suggested that any ADA impact is not driven by neutralizing activity. Collectively, this exploratory analysis suggests that the potential for ADA development should not impact treatment decisions with atezolizumab.
Insights
Anti-drug antibodies (ADA) development in patients receiving atezolizumab cancer therapy did not negatively impact treatment benefits. This study suggests ADA status should not influence clinical decisions for atezolizumab treatment.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Antibody therapeutics can elicit anti-drug antibodies (ADA), potentially affecting clinical outcomes.
- Evaluating ADA impact in oncology clinical trials requires robust methodologies to address confounding factors.
Purpose of the Study:
- To assess the efficacy and safety of atezolizumab in cancer patients based on ADA status.
- To investigate the influence of ADA on clinical outcomes in advanced cancer treated with atezolizumab.
Main Methods:
- Conducted adjusted meta-analyses accounting for baseline characteristics and survivorship bias.
- Pooled data from over 10 clinical trials evaluating atezolizumab in various advanced cancers.
- Performed unadjusted descriptive analyses on safety and adverse event data.
Main Results:
- Adjusted analyses showed ADA-positive patients still derived benefit from atezolizumab, especially in studies with an overall treatment effect.
- No clear relationship was identified between ADA status and the frequency or severity of adverse events in pooled analyses.
- Data indicated that ADA impact, if any, is not driven by neutralizing activity.
Conclusions:
- The development of anti-drug antibodies (ADA) should not deter treatment decisions for atezolizumab in oncology.
- Atezolizumab efficacy and safety appear consistent regardless of ADA status when confounding factors are addressed.
