Atezolizumab Stumbles in Triple Negative Breast Cancer Study: SABCS 2024 Results with Charles Geyer

In this presentation, Dr. Charles Geyer shares detailed results from the GeparDouze Phase III clinical trial (NSABP B59), which investigates the efficacy and safety of atezolizumab in combination with chemotherapy as neoadjuvant and adjuvant therapy for patients with Stage II and III triple-negative breast cancer (TNBC).

???? What You’ll Learn
The rationale for combining immune checkpoint inhibitors with chemotherapy in TNBC.
The significance of PD-L1 status and how it influenced trial outcomes.
Key comparisons between GeparDouze and the Keynote-522 study.
Adverse events observed, including immune-related toxicities like thyroid dysfunction, adrenal insufficiency, and colitis.
How evolving standard of care during the trial (e.g., capecitabine, olaparib) impacted results.
Subgroup analysis highlighting heterogeneity in patient outcomes.
Future directions, including efforts to identify biomarkers that predict response to immunotherapy.
???? Background and Rationale
Triple-negative breast cancer (TNBC) is highly aggressive and marked by genomic instability, high mutation burden, and immunogenic potential. The GeparDouze trial explored whether adding atezolizumab, an anti-PD-L1 checkpoint inhibitor, could augment the immune response and improve outcomes when combined with chemotherapy.

???? Key Results
PD-L1 status did not differentiate outcomes in this neoadjuvant setting, unlike in metastatic disease.
Patients with node-positive disease, larger tumors, or high tumor-infiltrating lymphocytes (TILs) appeared to derive the most benefit.
Survival rates in both arms were remarkably high, with 90% 4-year overall survival.
The trial highlighted the heterogeneity of TNBC and the need for precise biomarkers to optimize patient selection.
⚠️ Challenges and Takeaways
While the study did not show a survival benefit or alter the current standard of care, it underscores the complexity of TNBC and reinforces the importance of translational research. Biomarker discovery and refined patient selection may unlock the potential of immune checkpoint inhibitors like atezolizumab in future trials.

???? Chapters
0:00 Introduction
0:15 Standard of Care in Triple-Negative Breast Cancer
0:45 Immunogenicity and the Role of the Immune System
1:28 Rationale for Checkpoint Inhibitors
2:45 Overview of the GeparDouze Trial Design
3:30 PD-L1 Status and Its Impact on Results
4:15 Immune-Related Toxicities and Safety Findings
6:10 Differences Between GeparDouze and Keynote 522
7:00 Impact of Changing Standard of Care During the Study
8:15 Study Accrual and Challenges
9:30 Survival Rates and Long-Term Outcomes
11:00 Heterogeneity in Patient Outcomes and Subgroups
12:15 Future Directions: Biomarker Identification and Translational Research

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