2232O - Atezolizumab (atezo) and tumour microenvironment in early triple-negative breast cancer (eTNBC): Exploratory biomarker analysis from IMpassion031

Background

IMpassion031 showed that neoadjuvant chemotherapy (CT) + atezo significantly increased pathological complete response (pCR) and numerically favoured event-free, disease-free and overall survival (EFS, DFS and OS) vs CT + placebo (Pla) in patients (pts) with eTNBC. This IMpassion031 substudy assessed potential predictive tumour immune biomarkers for atezo clinical benefit.

Methods

Biomarker evaluation was performed on baseline, on-treatment, surgery and disease recurrence matched formalin-fixed, paraffin-embedded tumour tissue samples. Samples were tested for tumour infiltrating lymphocytes (TILs) and with RNA sequencing to derive molecular subtypes (basal-like immune activated [BLIA], basal-like immune suppressed [BLIS], mesenchymal [MES], luminal androgen receptor [LAR]), biological pathways and cellular components (xCELL). Biomarkers were evaluated for their association with pCR, EFS, DFS and OS.

Results

In patients with TIL-low tumours, atezo numerically improved outcomes compared with Pla (ΔpCR =19.4%, EFS hazard ratio [HR] 0.57, DFS HR 0.64 and OS HR 0.31). Atezo had higher pCR than Pla in BLIA (75% vs 54%) and BLIS (54% vs 32%) subtypes but not in LAR (33% vs 33%). While atezo showed improved EFS (HR 0.38) and DFS (HR 0.24) only in pts with BLIA tumours, atezo OS improvement vs Pla was only seen in pts with BLIS tumours (HR 0.17). The LAR subtype had excellent EFS, DFS and OS regardless of treatment, in contrast to a relatively low pCR rate. Biological pathway and cell type analyses indicated that increased proliferation, γδ T cells and pro-B cells predict atezo pCR benefit, while epithelial-mesenchymal transition, pericytes and stromal biology (e.g. angiogenesis, TGFβ) are linked to lack of atezo pCR benefit. No biological pathway or cell type consistently predicted atezo EFS, DFS or OS benefit. Exposure to CT ± atezo promoted dynamic changes in molecular subtype, which return to baseline at disease recurrence.

Conclusions

Atezo provides benefit in eTNBC pts with proliferative basal tumours, but is less active in indolent LAR tumours. Atezo improves outcomes in pts with low TILs, a subgroup with poor prognosis in eTNBC. Further studies are needed to validate these findings.

Clinical trial identification

NCT03197935.

Editorial acknowledgement

Research support for third-party writing assistance for this abstract, furnished by Katie Wilson, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

N. Harbeck: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, MSD, Novartis, Pierre Fabre, Pfizer, F. Hoffmann-La Roche Ltd., Seagen; Financial Interests, Personal, Other, Co-Director: West German Study Group (WSG); Financial Interests, Personal, Advisory Role: Comprehensive Cancer Center, Munich, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, F. Hoffmann-La Roche/Genentech, Inc., Sandoz, Seagen; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, MSD, F. Hoffmann-La Roche Ltd/Genentech, Inc. C. Duan: Non-Financial Interests, Personal, Funding, Research funding: Support for third party writing assistance from F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffman-La Roche Ltd., Bristol Myers Squibb. K. DuPree: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. C. Chang: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd. C.H. Barrios: Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: GSK, Novartis, Pfizer, Roche, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi; Financial Interests, Personal, Advisory Board, Consultation: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, Scientific Presentations Consulting AD Board: Daiichi Sankyo; Financial Interests, Personal, Ownership Interest, Virtual APP: Thummi; Financial Interests, Personal, Stocks/Shares, Clinical Research Company: MedSIR; Financial Interests, Institutional, Research Grant, Research Funding To The Institution: Pfizer, Amgen, GSK, Lilly, Sanofi, Merck, BioMarin, BMS, Medivation, Exelixis, Merck KGaA, Shanghai Henlius Biotech, Polyphor, PharmaMar; Financial Interests, Institutional, Research Grant, Research Funding to the Institution Steering Committee: Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Research Funding to the Institution Steering committee: Roche; Financial Interests, Institutional, Local PI, Research Funding to the institution: Nektar, Regeneron, Janssen, OBI Pharma, Seagen, Checkpoint Therapeutics, Novocure, Aveo Oncology, Takeda, Celgene, TRIO, PPD, Syneos health, DOCS, Labcorp, IQIVIA, Parexel, Nuvisan, PSI, Medplace; Financial Interests, Institutional, Local PI, Research funding to the institution Steering Committee: Myovant; Non-Financial Interests, Member of Board of Directors, Member of Executive Board: BIG International Group; Non-Financial Interests, Leadership Role, Latin American Cooperative Oncology Group: LACOG; Non-Financial Interests, Other, Chair, International Educational Steering Group: ASCO; Non-Financial Interests, Advisory Role, Member Compliance Committee: ESMO. H.A. Zhang: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd. S. Saji: Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai, AstraZeneca, Kyowa Kirin, Daiichi Sankyo, Taiho, Pfizer, MSD, Novartis, Eisai, Ono, Takeda, Exact Sciences; Financial Interests, Institutional, Research Grant: Taiho, Chugai, Daiichi Sankyo; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, Chugai, AstraZeneca, Sanofi; Non-Financial Interests, Member of Board of Directors: Japanese Breast Cancer Society, Japanese Society of Medical Oncology, Japan Breast Cancer Research Group, Breast International Group. K.H. Jung: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.: F Hoffmann-La Roche Ltd.; Financial Interests, Personal, Advisory Role: AstraZeneca, Bixink, Celgene, Daiichi Sankyo, Eisai, Everest Medicine, MSD, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche Ltd., Takeda Pharmaceuticals. M.L. Telli: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.; Financial Interests, Institutional, Research Grant: AbbVie, Arvinas, Bayer, Biothera, Calithera Biosciences, EMD Serono, Genentech, Inc., GSK, Hummingbird Biosciences, Medivation, Merck, Novartis, OncoSec, Pfizer, PharmaMar, Tesaro, Vertex; Financial Interests, Personal, Advisory Role: AbbVie, Aduro Biotech, AstraZeneca, Blueprint Medicines, Celgene, Daiichi Sankyo, Genentech/Roche, Gilead, GSK, G1 Therapeutics, Guardant, Immunomedics, Lilly, Merck, Natera, Novartis, OncoSec, Pfizer, RefleXion, Sanofi. M. Liste Hermoso: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche, Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche, Ltd. S. Chui: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. M. Dieterich: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. E.A. Mittendorf: Financial Interests, Personal, Advisory Board: Merck, BioNTech; Financial Interests, Institutional, Research Grant, I have a grant from SU2C funded by Roche/Genentech that supports the conduct of a clinical trial: Roche/Genentech; Financial Interests, Institutional, Coordinating PI, Gilead provides clinical trial support to my institution for a study that I am the PI on: Gilead; Financial Interests, Personal, Steering Committee Member: Roche/Genentech, BMS; Non-Financial Interests, Member of Board of Directors: American Society of Clinical Oncology; Non-Financial Interests, Advisory Role, I serve in an advisory role as a Komen Scholar: Komen for the Cure. L. Molinero: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: Roche/Genentech.