In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 573-573
Abstract:
573 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.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.573
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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