ASCO 2019 — Immune markers predict benefit of adjuvant pertuzumab in breast cancer


  • David Reilly
  • Oncology Conference reports
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Takeaway

  • Data from the largest biomarker analysis to date show that immune markers predict benefit of adjuvant pertuzumab in early-stage breast cancer.
  • Findings add to mounting evidence for an immune-mediated mechanism of action that may help shape future clinical trials in this setting.

Why this matters

  • The phase 3 APHINITY study demonstrated a modest improvement in invasive DFS (iDFS) with the addition of adjuvant pertuzumab to trastuzumab+chemotherapy.

Study design

  • Analysis of the APHINITY trial of patients with HER2+ breast cancer to investigate genomic correlates of response to adjuvant trastuzumab and pertuzumab.  
  • 1023 patient samples were evaluated.
  • Funding: Genentech; Pfizer.

Key results

  • The following were associated with inferior prognosis:
    • PI3K/PTEN/AKT pathway mutations: P=.04.
    • Amplification of MYC: P=.00.
    • Amplification of ZNF703: P=.02.
  • The following were associated with favorable prognosis:
    • TOP2A copy number amplifications, independent of treatment: P=.00.
    • Higher levels of TILs: P=.001.
    • HER2 copy number ≥6: P=.01.
  • PI3K/PTEN/AKT alterations, MYC, ZNF703, and TOP2A copy number amplifications were not predictive of pertuzumab benefit.
  • High levels of TILs and T-cell-related genes were predictive of greater pertuzumab benefit.

Limitations

  • Further analyses of immune-associated biomarkers are required.

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