306P - Multiplexed immunofluorescence (mIF) to select patients with HER2+ breast cancer (BC) having an excellent outcome without chemotherapy (chemo): A substudy of the PERNETTA trial (SAKK22/10-UCBG-BOOG)

Background

PERNETTA trial randomized 210 HER2+ BC patients (pts) to 1^st-line trasutuzmab-pertuzumab (T-P) alone or combined with chemo. In the final analysis (median follow-up 63 months), pts with chemo had longer progression free survival (PFS), but similar overall survival (OS) at 2 years. In this ancillary study, we aimed to identify immune biomarkers predicting for long PFS in pts with the chemo-free anti-HER2 strategy.

Methods

Six good and 6 poor responders were selected in each study arm, based on their PFS (total 24 pts); 77 proteins were assessed using GeoMx digital spatial profiling technology in these 24 samples, in the Immune Landscape Laboratory of the Ludwig Institute in Lausanne. Proteins discriminating good versus poor responders were selected to construct a panel of 7 proteins, which was then tested by mIF in the 142 available pts’ samples. After high-definition scanning, the tissue images were analyzed by IFQuant software and the results correlated with pts’ PFS and OS by stratification cox regression.

Results

CD8, GrzB, BCL2, CD44, MET, DAPI, and CK were selected for the final panel. In the chemo-free arm, pts with low expression of CD8-GrzB in stroma or CD8-MET in tumor had similar PFS as pts receiving chemo (p=0.8 and 0.4) and significantly better than the pts with high expressions (p=0.03 and 0.05). Pts without chemo and with low expression of CD8-MET in tumor showed a better OS than the pts with high expression (p=0.02) and even better than the pts having received chemo (p=0.04). In addition, different combined expressions of these biomarkers in stroma and in tumor were able also to discriminate pts with good versus poor outcome in arm A, arm B or whole study population.

Conclusions

Immunity plays a significant role in the efficacy of anti-HER2 treatments. mIF allowing to assess simultaneously several biomarkers presence, intensity and location seems to permit selecting pts with HER2+ advanced stage BC having an excellent outcome in terms of PFS and OS without chemo in 1^st line. If validated these biomarkers may contribute to treatment de-escalation and quality of life improvement.

Clinical trial identification

CHUV_DO_CTE_TRP_0001_2017 Ethical committe agreement: 15/07/2021.

Editorial acknowledgement

No

Legal entity responsible for the study

Lausanne University Hospital, Prof. Lana Kandalaft.

Funding

Roche provided an unrestricted funding.

Disclosure

K. Zaman: Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi, Lilly, Pierre Fabre, Gilead, MSD, Novartis, Seagen, Viatris; Financial Interests, Institutional, Funding, Translational study: Roche; Financial Interests, Institutional, Steering Committee Member: Pierre Fabre; Financial Interests, Institutional, Other, Member of the IDMC of an international trial: Roche; Financial Interests, Institutional, Steering Committee Member, Member of the Steering committee of an international study: Daiichi; Non-Financial Interests, Advisory Board: Swiss Group for Clinical Research Against Cancer (SAKK), Executive Committee of the MINDACT trial; Non-Financial Interests, Member, Representative of SAKK Breast Group: Breast International Group (BIG); Non-Financial Interests, Member: EORTC Breast Group; Other, Unrestricted funding for organization of academic symposium: Agendia, AstraZeneca-MSD, Daiichi, Eisai, Exact Sciences, Lilly, Pierre Fabre, Gilead, Novartis, Pfizer, Roche, Seagen, Viatris, Vifor; Other, Support for participation in international congress: AstraZeneca, Daiichi, Gilead, Pierre Fabre, Roche, Lilly. J. Huober: Financial Interests, Institutional, Research Funding: Celgene, Novartis, Lilly; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, AbbVie, Seagen, Gilead, Daiichi; Financial Interests, Institutional, Advisory Board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, AbbVie, Seagen, Gilead; Financial Interests, Institutional, Other, travel grant: Roche, Pfizer, Novartis, Daiichi. P. Weder: Financial Interests, Institutional, Other, travel grants: Roche. All other authors have declared no conflicts of interest.