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Proffered Paper session 2

LBA2 - Impact of RNA expression signatures and tumor infiltrating lymphocytes (TILs) for pathological complete response (pCR) and survival after 12 week de-escalated neoadjuvant pertuzumab + trastuzumab ± paclitaxel in the WSG-HER2+/HR- ADAPT trial.

Date

08 May 2021

Session

Proffered Paper session 2

Presenters

Monika Graeser

Citation

Annals of Oncology (2021) 32 (suppl_2): S48-S53. 10.1016/annonc/annonc505

Authors

M. Graeser

Author affiliations

  • Mönchengladbach/DE
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Resources

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Abstract LBA2

Background

Limited data are available on predictive biomarkers for dual anti-HER2 blockade in HER2+/HR- early breast cancer (BC). The present analysis aimed to identify associations of biological signatures and stromal TILs (sTILs) with pCR and survival in phase II WSG-ADAPT HER2+/HR- trial (NCT01779206).

Methods

Patients (pts) with cT1-cT4c, cN0-3 HER2+/HR- BC were randomized to receive pertuzumab + trastuzumab (P+T) in Arm A (n=92) or P+T+paclitaxel in Arm B (n=42). Gene expression signatures were analyzed in baseline (BL) biopsies using NanoString Breast Cancer 360 panel (n=117); BL and on-treatment (week 3) sTIL levels were available in 119 and 76 pts, respectively. Impacts of standardized gene expression signatures on pCR (odds ratios, OR) and invasive disease-free survival (iDFS; hazard ratios, HR) were estimated by logistic and Cox regression, respectively; Spearman correlations were computed.

Results

In all pts, ERBB2 (OR 1.7; 95%CI 1.1-2.7) and estrogen receptor (ER) pathway signaling signatures (OR 1.7; 95%CI 1.1-2.6) were favorable, while PTEN signature (OR 0.6; 95%CI 0.4-0.9) was unfavorable for pCR. After 60 months median follow-up, 13 (A: 11, B: 2) invasive events occurred, none following pCR (ypT0 ypN0). Regarding iDFS, several gene signatures related to immune response (IR) as well as ER signaling were favorable, all with similar HR about 0.4 - 0.6. These patterns were even more prominent in the neoadjuvant chemotherapy-free Arm A, where additionally, BRCAness signature was unfavorable (HR 2.0; 95%CI 1.0-3.8). All significant IR signatures were strongly intercorrelated. sTILs (BL/week 3/change) were not significantly associated with pCR or iDFS, though BL-sTIL correlated positively with IR signatures.

Conclusions

The present translational analysis of the WSG-ADAPT HER2+/HR- trial suggests distinct (except for ER signaling) gene signatures associated with pCR vs iDFS. IR signatures can augment morphological data from sTILs; the potential role of IR in preventing recurrence suggests that pts with up-regulated IR signatures could be candidates for de-escalation concepts in HER2+ BC.

Clinical trial identification

EudraCT Number: 2011-001462-17.

Legal entity responsible for the study

Westdeutsche Studiengruppe GmbH.

Funding

Hoffmann la Roche.

Disclosure

All authors have declared no conflicts of interest.

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