In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 4_Supplement ( 2019-02-15), p. GS5-06-GS5-06
Abstract:
Background:Immune markers such as tumor infiltrating lymphocytes (TILs), CD8, PDL1, PD1 and other protein or mRNA-based genomic markers have been identified as prognostic / predictive in TNBC regarding survival / chemotherapy (CTx) efficacy. In the adjuvant WSG-PlanB trial, patients with high TILs and/or CD8 by mRNA had excellent outcome, irrespective of anthracycline use; in the neoadjuvant ADAPT-TN trial, high PDL1, PD1 and CD8 and/or TILs were predictive for pCR. Still, optimal markers for potential treatment de-escalation have yet to be determined. Here, we analyse for the first time impact of immune mRNA-based markers and TIL's as prognostic and predictive survival markers. Methods: TNBC patients (ER/PR & lt;1%, HER2-,) were randomized to neoadjuvant 4x nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1/8 q3w (gem arm) or 4x nab-paclitaxel 125 mg/m2/carboplatin AUC2 day 1/8 3-weekly (q3w) (carbo arm). Primary endpoint of WSG-ADAPT-TN was pCR (ypT0/is/ypN0); secondary endpoints included translational analyses, e.g., TILs or expression of 119 genes by nCounter platform. Standard adjuvant chemotherapy (4xEC) was optional (not randomized) in patients achieving pCR after 12 weeks. According to protocol, 1st safety survival analysis was performed after 3y median follow-up. Results: Present translational analysis included 306 of 336 TNBC patients (36 months median FU). pCR was associated with significantly better survival (3y EFS: 92% vs. 71%, p & lt;.001), but despite substantially higher pCR in the carbo arm (46% vs. 29%), no significant EFS advantage was seen (p=.6) (gem: 78%; carbo: 80%; 3y-EFS). Bivariate Spearman correlations among CD8, PD1, and PDL1 were strongly positive; their correlations with TILs were moderately positive. Preliminary Cox analysis of EFS was performed with clinical variables (cN, cT, menopausal status); neoadjuvant study arm; pCR; TILs; proliferation markers (baseline Ki67 by IHC, scores derived from PAM50); baseline immune markers; risk scores; and individual gene expression scores previously identified as prognostic for pCR in one or both neoadjuvant arms. Independent prognostic factors included pCR, cN, Ki67, PD1, and CD8; these were entered into (prognostic) interaction analysis. The resulting model contained cN, high Ki67 and low TILs as (unfavorable) main effects and the interaction of (higher) PD1*pCR (favorable). Among pCR patients, the groups with/without additional adjuvant CTX were similar with respect to explanatory factors. Baseline TILs, Ki67, cN, and PD1 were entered into exploratory predictive analysis; the model retained only the interaction [adjuvant CTx * (fractionally ranked) PD1]. In patients with pCR, those with low PD1 benefited from standard anthracycline-containing adjuvant CTx, whereas patients high PD1 did not with an 98% 3y-EFS. Conclusions: Our exploratory results suggest independent prognostic impact of mRNA markers and TIL's in early TNBC. Patients with both pCR (after 12 weeks) and “high-immune” signature (defined here by PD1) had excellent 3y-EFS and may be candidates for treatment de-escalation (e.g. omission of anthracyclines), whereas “low-immune” pCR patients may benefit from standard adjuvant poly-chemotherapy. Citation Format: Gluz O, Nitz U, Liedtke C, Prat A, Christgen M, Feuerhake F, Garke M, Grischke E-M, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Kuemmel S, Pelz E, Gebauer D, Paré L, Kates R, Wuerstlein R, Kreipe HH, Harbeck N. No survival benefit of chemotherapy escalation in patients with pCR and “high-immune” triple-negative early breast cancer in the neoadjuvant WSG-ADAPT-TN trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS5-06.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.SABCS18-GS5-06
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2019
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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