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Attend this session at the
2019 ASCO Annual Meeting!

Session: Targeting Breast Cancer: Breaking the Code

Type: Clinical Science Symposium

Time: Saturday June 1, 3:00 PM to 4:30 PM

Location: Hall D1

Genomic correlates of response to adjuvant trastuzumab (H) and pertuzumab (P) in HER2+ breast cancer (BC): Biomarker analysis of the APHINITY trial.


Breast Cancer—Metastatic

2019 ASCO Annual Meeting

Abstract No:

J Clin Oncol 37, 2019 (suppl; abstr 1012)

Author(s): Ian E. Krop, Joseph Paulson, Christine Campbell, Astrid Christina Kiermaier, Fabrice Andre, Debora Fumagalli, Sanne de Haas, Roberto Salgado, Carsten Denkert, Sibylle Loibl, Andrew Bailey, Gail Lewis Phillips, Elizabeth Frank, Martine Piccart, Giuseppe Viale, Sherene Loi; Dana-Farber Cancer Institute, Boston, MA; Genentech, San Francisco, CA; Frontier Science Scotland, Kingussie, United Kingdom; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Institut Gustave Roussy, Villejuif, France; Breast International Group, Brussels, Belgium; NSABP/NRG Oncology and Peter MacCallum Cancer Centre, East Melbourne, Australia; Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum Marburg, Marburg, Germany; German Breast Group (GBG) and Centre for Haematology and Oncology Bethanien, Frankfurt, Neu-Isenburg, Germany; Frontier Science, Kincraig Inverness-Shire, United Kingdom; Genentech, South San Francisco, CA; Institut Jules Bordet, Brussels, Belgium; Division of Pathology, European Institute of Oncology, IRCCS, Milan, Italy; Peter MacCallum Cancer Centre, Melbourne, Australia

Abstract Disclosures


Background: We conducted a comprehensive genomic and immune-marker based analysis to identify prognostic and predictive biomarkers beyond clinical parameters (eg nodal status) in the setting of HP-based therapy. Methods: APHINITY, a phase III study, randomized 4805 pt with HER2+ BC to adjuvant chemo/H, plus P or placebo. Tumor Infiltrating Lymphocytes (TILs) were analysed using published methods. A nested case-control design with 1023 pt samples (3 controls matched to 1 distant relapse) underwent DNA (targeted) and RNA sequencing. Inverse probability weighting with Kaplan-Meier estimator weights, and models adjusted for treatment, hormone receptor, nodal status, age and chemotherapy type were used. Results are reported descriptively with 95% CIs. Interaction p-values are unadjusted for multiplicity. Results: DNA-seq, RNA-seq and TIL analyses were successful in 940/1023 (92%), 974/1023 (95%), and 4313/4804 (90%) samples, respectively. Prognosis (arms pooled): PI3K/PTEN/AKT alterations (HR 1.35; CI 1.01-1.79), MYC (HR 1.61; CI 1.16-2.23) or ZNF703 amplification (HR 1.62; CI 1.07-2.47) suggest poorer prognosis while TOP2A amplification (HR 0.49; CI, 0.32-0.74) suggests better prognosis independent of anthracycline use. Higher mRNA expression of an immune signature (IFNG, PD-L1, CXCL9 (HR 0.68; CI 0.52-0.89)) and TILs (HR 0.91; CI 0.86-0.96) also suggest better outcomes. Predictive effects: Table shows the HR for H+P benefit versus H for selected markers. PAM50 subtype did not predict benefit. Conclusions: In this comprehensive biomarker analysis, higher levels of immune markers and HER2 appeared to be associated with better prognosis and greater H+P benefit. Clinical trial information: NCT01358877

NBiomarker +
HR (95% CI)
NBiomarker -
HR (95% CI)
TILs > 75th %ile9880.35 (0.19-0.65)33250.95 (0.75-1.20)0.003
IFNG > 75th %ile2400.45 (0.24-0.83)7300.96 (0.71-1.30)0.029
CXCL9 > 75th %ile2400.49 (0.27-0.89)7300.95 (0.70- 1.28)0.054
PD-L1 > 75th %ile2400.52 (0.28-0.99)7300.91 (0.68-1.23)0.121
HER2 CN > = 642970.75 (0.60-0.93)5071.41 (0.80-2.47)0.039
HER2 IHC3+43670.76 (0.61-0.94)4371.40 (0.74-2.66)0.075
PI3K/PTEN/AKT alt3121.20 (0.76-1.89)6270.74 (0.53-1.05)0.102

Other Abstracts in this Sub-Category:


1. SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx).

Meeting: 2019 ASCO Annual Meeting Abstract No: 1000 First Author: Hope S. Rugo
Category: Breast Cancer—Metastatic - HER2-Positive


2. Pyrotinib combined with capecitabine in women with HER2+ metastatic breast cancer previously treated with trastuzumab and taxanes: A randomized phase III study.

Meeting: 2019 ASCO Annual Meeting Abstract No: 1001 First Author: Zefei Jiang
Category: Breast Cancer—Metastatic - HER2-Positive


3. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 1002 First Author: Cristina Saura
Category: Breast Cancer—Metastatic - HER2-Positive