In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 510-510
Abstract:
510 Background: In TNBC, the interplay between immunophenotype, tumor proliferation (prolif) and achievement of pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) remains unknown. Methods: RNA seq was performed on pre-tx research biopsies of stage II/III TNBC enrolled in BrighTNess. NAC regimens included paclitaxel alone or with carboplatin (Cb) or Cb plus veliparib, followed by AC. Computational analysis included subtyping (i.e. PAM50, Pietenpol), prolif (PAM50) and GeparSixto immune signature (GSIS). Cb-containing arms were combined due to similar pCR. Results: High quality RNA seq data was obtained from 482 of 634 pts. PAM50 classified 80.1% of tumors as basal-like. TNBC subtypes were mostly BL1 or BL2 (23.3%), IM (22.4%) or M/MSL (31.7%); 6% were LAR. pCR was higher for basal vs non-basal tumors (52.3% vs 35.4%, p = 0.003). IM had the highest pCR rate (64.2%, 95% CI 59.9%,68.5%). Basal-like was not a significant predictor for Cb benefit (p-interaction = 0.8). Prolif (OR = 0.30 p 〈 0.001) and GSIS (OR 0.68 p 〈 0.001) were significantly correlated with pCR but did not correlate with each other (Pearson’s r2 = 0.027). In multivariate analysis, prolif (HR = 0.36 95% CI, 0.21-0.61 p = 0.0002) and GSIS (HR = 0.62 95% CI, 0.49-0.79 p 〈 0.0001) increased the ability to predict pCR beyond standard clinico-pathologic variables (likelihood ratio = 14.9, p = 0.0001115). Among all pts, those above the median for both prolif. and GSIS had the highest pCR (67%; 84/125) while those below the median for both had the lowest pCR rate (34%; 42/125). Tumors with higher inferred CD8 + T-cell infiltration demonstrated greater benefit from Cb using either TIMER (HR = 0.83 [0.73-0.95]) or CIBERSORT (HR = 0.83 [0.76-0.91] ). Tumors with higher inferred total macrophages, particularly immune suppressive M2 macrophages had a higher pCR rate on the non-Cb arm (AC-T) using CIBERSORT (HR = 1.27 [1.07,1.50]). Conclusions: Immunophenotype and proliferation are independent predictors of pCR to standard NAC regimens in TNBC. PAM50 is not a significant predictor of Cb benefit. Exploratory findings suggest that tumor infiltrating immunophenotype (i.e. CD8 T cells and macrophages) may predict response to specific NAC regimens in TNBC. Clinical trial information: NCT02032277.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.510
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
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