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Clinical Trial
. 2020 Jan 1;146(1):262-271.
doi: 10.1002/ijc.32488. Epub 2019 Jun 19.

Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple-negative early breast cancer: Primary translational analysis of the WSG-ADAPT-TN trial

Oleg Gluz  1   2   3 , Cornelia Kolberg-Liedtke  4 , Aleix Prat  5   6 , Matthias Christgen  7 , Daniel Gebauer  8 , Ronald Kates  1 , Laia Paré  5   6 , Eva-Maria Grischke  9 , Helmut Forstbauer  10 , Michael Braun  11 , Mathias Warm  12 , John Hackmann  13 , Christoph Uleer  14 , Bahriye Aktas  15   16 , Claudia Schumacher  17 , Sherko Kuemmel  18 , Rachel Wuerstlein  1   19 , Enrico Pelz  8 , Ulrike Nitz  1   2 , Hans Heinrich Kreipe  7 , Nadia Harbeck  1   19
Affiliations
Clinical Trial

Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple-negative early breast cancer: Primary translational analysis of the WSG-ADAPT-TN trial

Oleg Gluz et al. Int J Cancer. .

Abstract

In the neoadjuvant WSG-ADAPT-TN trial, 12-week nab-paclitaxel + carboplatin (nab-pac/carbo) was highly effective and superior to nab-paclitaxel + gemcitabine (nab-pac/gem) in triple-negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients received 4 × nab-pac 125 mg/m2 (plus carbo AUC2 or gem 1,000 mg/m2 d1,8 q21). Expression of 119 genes and PAM50 scores by nCounter were available in 306/336 pretherapeutic samples. Interim survival analysis was planned after 36 months median follow-up. Basal-like (83.3%) compared to other subtypes was positively associated with pCR (38% vs. 20%, p = 0.015), as was lower HER2 score (p < 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all p < 0.004), higher Ki-67 (IHC; p < 0.001). For nab-pac/carbo, expression of immunological (CD8, PD1 and PFDL1) genes and proliferation markers (proliferation and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3 and TYMS) were positively associated with pCR (p < 0.05 for all). For nab-pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: p = 0.05; FGFR4: p = 0.02; VEGFA: p = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event-free survival: 92% vs. 71%, p < 0.001). In early TNBC, basal-like subtype, higher Ki-67 (IHC) and lower HER2 score were, associated with chemosensitivity. Chemoresistance pathways differed between the two taxane based combinations. Combination of proliferation/immune markers and PAM50 subtype could allow patient selection for further deescalated chemotherapy and/or immune treatment approaches.

Keywords: ADAPT; HER2; PAM50; TNBC; carboplatin; deescalated chemotherapy; gemcitabine; immune markers; nab-paclitaxel.

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References

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