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Abstract LB162: Evaluation of tumor immune biomarkers with pathologic complete response (pCR) in patients receiving atezolizumab + chemotherapy in early triple negative breast cancer (eTNBC): exploratory analyses from the IMpassion031 study

2021; American Association for Cancer Research; Volume: 81; Issue: 13_Supplement Linguagem: Inglês

10.1158/1538-7445.am2021-lb162

1538-7445

Luciana Molinero, Elizabeth A. Mittendorf, Hong Zhang, Carlos H. Barrios, Shigehira Saji, Kyung Hae Jung, Shilpen Patel, Ching‐Wei Chang, Mario Liste-Hermoso, Jane Yuet Ching Hui, Nadia Harbeck,

Ferroptosis and cancer prognosis

Abstract Background: Biomarkers of tumor immunity have been associated with the clinical activity of immune checkpoint inhibitors in TNBC. IMpassion031 showed improvements in pCR in eTNBC with neoadjuvant atezolizumab (A) plus nab-paclitaxel (nP) followed by A with doxorubicin/cyclophosphamide (AC) in patients (pts) with high-risk primary invasive eTNBC regardless of PD-L1 status (Mittendorf et al, Lancet 2020). The current study evaluated the association of tumor immune biomarkers with A plus chemotherapy pCR rates and on-treatment modulation. Methods: IMpassion031 (NCT03197935) is a Phase III, global, double-blind, randomized trial. Eligible pts (≥18 years old) had previously untreated, stage II-III (cT2-T4d and cN0-N3c) invasive eTNBC. Pts (N=333) were randomized 1:1 to receive A 840 mg or placebo (P) every 2 weeks (q2w) + nP 125 mg/m2 weekly for 12 weeks, followed by A 840 mg or P q2w + doxorubicin 60 mg/m2 q2w and cyclophosphamide 600 mg/m2 q2w for 4 doses, before undergoing surgery. Evaluable samples collected at baseline (N=333 [mandatory]) and on treatment (OT, n=27 [optional]) were assessed for PD-L1 expression (VENTANA SP142) on immune (IC) and tumor (TC) cells, levels of stromal and intratumoral tumor-infiltrating lymphocytes (sTILs, iTILs) and the presence of tertiary lymphoid structures (TLS). Dynamics and association with pCR were also evaluated. Results: PD-L1 IC, PD-L1 TC, sTIL and iTIL levels were balanced between treatment arms. 46% of pts were PD-L1 IC+ (IC≥1%) and 16% of pts were PD-L1 TC+ (TC≥1%); most of the latter were also IC+. PD-L1 IC was weakly correlated with sTILs (r=0.33) or iTILs (r=0.30). pCR increased at higher PD-L1 IC cutoffs regardless of treatment arm and was higher in the A arm (PD-L1 IC<1%: 48%; ≥1% and <5%: 62%; ≥5%: 85%) than the P arm (35%, 40% and 67%, respectively). A numerically higher pCR difference favoring A vs P was observed in PD-L1 TC+ pts (76% vs 55%) vs TC- pts (54% vs 39%). Neither elevated sTILs, iTILs or TLS were associated with increased pCR in the A arm, though these biomarkers were linked to improved pCR in the P arm. Evaluation of OT biopsies suggested that the addition of A to nP elevated PD-L1 IC, TC and iTILs, but not sTILs, while P + nP mildly increased PD-L1 IC but not the other biomarkers tested. Increases in PD-L1 IC and iTILs 2 weeks post-treatment initiation were linked to pCR in A only. Conclusions: Several tumor immune biomarkers were associated with each other and with improved pCR in the IMpassion031 control arm, but only PD-L1 expression on IC or TC was linked to numerically increased pCR rates with A + nP-AC. Preliminary on-treatment data suggest that A plus chemotherapy promotes close contact of lymphocytes with tumor cell nests. Further evaluation of the tumor immune microenvironment in pts treated with A + nP-AC is warranted. Citation Format: Luciana L. Molinero, Elizabeth A. Mittendorf, Hong Zhang, Carlos H. Barrios, Shigehira Saji, Kyung Hae Jung, Shilpen Patel, Ching-Wei Chang, Mario Liste-Hermoso, Stephen Y. Chui, Nadia Harbeck. Evaluation of tumor immune biomarkers with pathologic complete response (pCR) in patients receiving atezolizumab + chemotherapy in early triple negative breast cancer (eTNBC): exploratory analyses from the IMpassion031 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB162.