Association of molecular subtype, proliferation, and immune genes with efficacy of carboplatin versus gemcitabine addition to taxane-based, anthracycline-free neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC): Results of the randomized WSG ADAPT-TN trial.

Authors

null

Oleg Gluz

West German Study Group, Moenchengladbach, Germany

Oleg Gluz , Cornelia Liedtke , Aleix Prat , Matthias Christgen , Daniel Gebauer , Ronald E. Kates , Eva-Maria Grischke , Helmut Forstbauer , Michael Wilhelm Braun , Mathias Warm , John Hackmann , Christoph Uleer , Bahriye Aktas , Claudia Schumacher , Sherko Kummel , Rachel Wuerstlein , Enrico Pelz , Ulrike Nitz , Hans Heinrich Kreipe , Nadia Harbeck

Organizations

West German Study Group, Moenchengladbach, Germany, University of Schleswig-Holstein Campus Luebeck, Lübeck, Germany, Medical Oncology Department. Hospital Clinic, Barcelona, Spain, Hannover Medical School, Hannover, Germany, Institute of Pathology, Viersen, Germany, REK Consulting, Otterfing, Germany, Universitӓts-Frauenklinik Tubingen, Eberhard Karls University, Tubingen, Germany, Praxisnetzwerk Hamatologie / intern. Onkologie, Troisdorf, Germany, Rotkreuzklinikum, Munich, Germany, Hopital Holweide, Cologne, Cologne, Germany, Marienhospital Witten, Witten, Germany, Gynecology Practice, Hildesheim, Germany, University Hospital Essen, Essen, Germany, St. Elisabeth Hospital Köln-Hohenlind, Cologne, Germany, Breast Unit, Kliniken Essen-Mitte, Essen, Germany, LMU Munich, Munich, Germany, Institute for Pathology, Viersen, Germany, West German Study Group, Evangelic Hospital Bethesda, Moenchengladbach, Germany, Breast Centre LMU Munich, Munich, Germany

Research Funding

Pharmaceutical/Biotech Company

Background: In the ADAPT-TN neoadjuvant trial, 12-week nab-paclitaxel (nab- pac)+carboplatin (carbo) was highly effective and superior to nab-pac+gemcitabine (gem). However, within TNBC, reliable predictive markers for carbo use have yet to be identified. Methods: Patients with early TNBC (centrally confirmed) were treated by nab-pac 125 mg/m2 with either carbo AUC2 or gem 1000 mg/m2 d 1,8 q21 given for 4 cycles. Genomic data (80 genes) and Prosigna (PAM-50) scores were available in 306 pre-therapeutic samples of 331 treated patients. Fisher’s exact test was performed for pCR differences; associations of continuous measurements or scores with pCR were analyzed by the Mann-Whitney statistic. Results: pCR was 44.5% to 28.4% (p=.004) in favor of nab-pac - carbo. Specifically within the carbo- containing arm, immunological (CD8, PD1, PFDL1) genes and proliferation markers (proliferation score and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3, TYMS) were positively associated with pCR (p<.05 for all). Specifically within the gem-arm, angiogenesis genes were negatively associated with pCR (ANGPTL4: p=.05; FGFR4: p=.02; VEGFA: p=.03). In the whole collective, basal-like (83.3%) was favorable for pCR (38% vs. 20%, p=.015) compared to other subtypes (HER: 6.4%; luminal-A: 1.7%; normal: 8.7%), as was lower HER-2 score (p<.001). Proliferation was positively associated with pCR: i.e., Pam50 proliferation score, ROR scores (all p<.004), and higher Ki67 by central IHC (p<.001) -- though not MKI67 RNA expression, despite their moderate correlation. Conclusions: In early TNBC, basal-like subtype, higher Ki67 (by IHC), and lower HER-2 score were associated with chemo-sensitivity for both neoadjuvant arms. Chemo-resistance pathways differed between the two taxane-based combinations (low proliferation and immune marker gene expression for carbo, high angiogenesis for gem). The positive predictive impact of immunological genes in the nab-pac - carbo arm could influence optimal patient selection for immune-modulative therapy. Clinical trial information: NCT01815242

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—Local/Regional/Adjuvant

Track

Breast Cancer

Sub Track

Neoadjuvant Therapy

Clinical Trial Registration Number

NCT01815242

Citation

J Clin Oncol 35, 2017 (suppl; abstr 573)

DOI

10.1200/JCO.2017.35.15_suppl.573

Abstract #

573

Poster Bd #

173

Abstract Disclosures