LBA19 - Event-free survival (EFS) analysis of neoadjuvant taxane/carboplatin with or without atezolizumab followed by an adjuvant anthracycline regimen in high-risk triple negative breast cancer (TNBC): NeoTRIP Michelangelo randomized study

Background

In NeoTRIP (NCT002620280) addition of atezolizumab to nab-paclitaxel/carboplatin was linked to minor numerical increase of pathologic complete response (pCR) in women with high-risk TNBC (48.6 vs 44.4%, p = 0.48), which was 7.6% higher in PD-L1 positive tumors treated with atezolizumab (Gianni L et al, Annal Oncol 2022).

Methods

In the phase III open label NeoTRIP study 280 patients with early high-risk or locally advanced TNBC were randomized to neoadjuvant carboplatin AUC 2 and nab-paclitaxel 125 mg/m² iv on d1,8 q3 wks with (138) or w/o (142) atezolizumab 1200 mg iv on d1, for 8 cycles followed by surgery and by 4 cycles of an anthracycline regimen regardless of pCR. The primary endpoint of the study is EFS, defined as time from date of randomization to date of disease progression while on primary therapy, or disease recurrence after surgery or death due to any cause.

Results

At median follow-up of 54 months, the five-year EFS was 70.6% (95% CI 61.6 – 77.9) with atezolizumab and 74.9% (95% CI 66.6 – 81.5) w/o atezolizumab. The stratified analysis (by disease stage, PD-L1, age class) resulted in a p-value = 0.66. The table shows the impact of the stratification factors and pCR on EFS evaluated by a multivariate Cox model. Higher baseline stromal TILs were prognostic of better EFS in each arm, but they were not predictive of atezolizumab benefit. No new safety signals possibly related to atezolizumab emerged during follow up. Table: LBA19

Conclusions

In NeoTRIP the addition of neoadjuvant atezolizumab to carboplatin/nab-paclitaxel did not improve EFS of patients with TNBC. PD-L1 expression and higher sTILs at baseline were prognostic for better EFS, but not predictive of atezolizumab benefit. Extensive biomarkers analysis by Image Mass Cytometry (Wang XQ et al, Nature 2023), RNAseq and WES are ongoing to identify those cases who can derive benefit from atezolizumab.

Clinical trial identification

NCT002620280, EudraCT 2014-005017-23.

Editorial acknowledgement

Legal entity responsible for the study

Fondazione Michelangelo.

Funding

Supported in part by unrestricted grants from Hoffman-La Roche, Ltd, Switzerland and Celgene, a Bristol Myers Squibb Company, Switzerland.

Disclosure

L. Gianni: Financial Interests, Personal, Advisory Board: AstraZeneca, Celgene, Roche, Zymeworks, Artemida Pharma Ltd, Pfizer; Financial Interests, Personal, Other, Consultant: Zymeworks, Metis Precision Medicine, Revolution Medicines, Menarini Ricerche, Amgen, Biomedical Insights Inc, Novartis; Financial Interests, Personal, Invited Speaker, Speaker at TIBCS 2020 Annual Conference-Virtual: Roche Products Ltd; Non-Financial Interests, Other, Chair Breast Cancer Research Committee Fondazione Michelangelo: Fondazione Michelangelo; Other, Co-inventor of European Patent Application N. 12195182.6 and 12196177.5 titled: Roche. C. Huang: Financial Interests, Institutional, Invited Speaker, Speakers bureaus: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, speakers bureaus: AstraZeneca, Pfizer, Novartis, Roche, Eli Lilly, Gilead; Financial Interests, Institutional, Research Grant, research grants to institution: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Research grants to institution.: AstraZeneca, EirGenix, Eli Lilly, MSD, OBI Pharma, Pfizer, Roche, Novartis, Seagen, Gilead, Aston Sci; Non-Financial Interests, Advisory Role, Advisory boards: Daiichi Sankyo, AstraZeneca, Eli Lilly, Pfizer, Novartis, Roche. D. Egle: Financial Interests, Personal, Advisory Board: AstraZeneca, Gilead, Pfizer, Novartis, Daiichi Sankyo, Lilly, Seagen, Pierre-Fabre, MSD; Financial Interests, Personal, Invited Speaker: Roche, Sirius Medical. B. Bermejo: Financial Interests, Personal, Invited Speaker: Novartis, Lilly, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Segaen, RochE, Gilead. C. Zamagni: Financial Interests, Personal, Advisory Board: Roche, Eisai, Novartis, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Exact Sciences, MSD, GSK, Gilead, Seagen; Financial Interests, Institutional, Local PI: Roche, Novartis, AstraZeneca, Pfizer, Seagen, Medivation, AbbVie, Array BioPharma, Morphotek, Synthon, Daiichi Sankyo, MSD, GSK, Gilead; Financial Interests, Personal, Other, Member of an Independent Data Monitoring Committee for an international clinical trial: AstraZeneca; Non-Financial Interests, Other, member of the Scientific Committee: LOTO Onlus, Susan J Komen Emilia-Romagna, Mamazone Sudtirol; Other, travel accomodation and partecipation expenses for scientific congresses: Roche, Novartis, Pfizer, Daiichi Sankyo, MSD, GSK, Gilead, AstraZeneca. M. Thill: Financial Interests, Personal, Advisory Board: Agendia, AstraZeneca, Becton and Dickinson, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Novartis, Onkowissen, Organon, Pfizer, pfm medical, Pierre Fabre, Roche, Seagen, Vifor, Viatris; Financial Interests, Personal, Invited Speaker: Agendia, Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, GSK, Lilly, MSD, Neodynamics, Novartis, Pfizer, pfm medical, Roche, Seagen, Sirius Medical, Sirius Medical, Laborarztpraxis Walther, Jörg Eickeler, Vifor; Financial Interests, Personal, Writing Engagement, Manuscript support: Amgen; Financial Interests, Personal, Other, Travel expenses and congress support: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Aurikamed, Gilead Science, Lilly, MSD, Novartis, Pfizer, pfm medical, Seagen; Financial Interests, Personal, Other, Video statement: GSK; Financial Interests, Personal, Other, Congress support and travel expenses: Neodynamics, Pierre Fabre, Sirius Medical; Financial Interests, Personal, Writing Engagement: Servier, ClearCut; Financial Interests, Personal, Other, writing support: pfm medical; Financial Interests, Personal, Member of Board of Directors: AWOgyn, DGGG; Financial Interests, Institutional, Local PI: AstraZeneca, Novartis, Roche, Endomag, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: ClearCut, Neodynamics, RTI Surgical; Financial Interests, Institutional, Research Grant: Exact Sciences; Financial Interests, Institutional, Steering Committee Member: pfm medical, Novo Scientific; Non-Financial Interests, Member of Board of Directors: OncoNet Rhein-Main. A. Anton Torres: Financial Interests, Personal, Invited Speaker: AstraZeneca-Daiichi Sankyo, Eli Lilly, Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca-Daiichi Sankyo, Eli Lilly, Gilead, Pfizer, Eli Lilly. G. Bianchini: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Roche, Amgen, MSD, Chugai, Eisai, Gilead, Seagen, Exact Science, Roche, MSD, Gilead; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Daiichi Sankyo, Roche, MSD, Gilead, Sanofi; Financial Interests, Personal, Invited Speaker: Lilly, Roche, AstraZeneca, Daiichi Sankyo, MSD, Chugai, Eisai, Gilead, Seagen, Neopharm Israel; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Chugai, Novartis, Gilead, Daiichi Sankyo, Roche, Pfizer, MSD; Financial Interests, Personal and Institutional, Steering Committee Member: Roche, AstraZeneca, Novartis, Lilly; Financial Interests, Institutional, Local PI: Lilly, Gilead, Pfizer, Daiichi Sankyo, MSD, Novartis; Non-Financial Interests, Leadership Role, Head of Traslational Research: Fondazione Michelangelo. E. Sevillano Fernandez: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Coordinating PI: Pfizer. E.M. Ciruelos: Financial Interests, Personal, Other, Speakers Bureau. Educational activities: Roche; Financial Interests, Personal, Invited Speaker, Symposia and Educational activities: Roche; Financial Interests, Personal, Advisory Board, Non-permanent advisor: Roche, Lilly, Novartis, Pfizer, Daiichi Sankyo, MSD; Financial Interests, Personal, Invited Speaker, Symposia and Education: Lilly; Financial Interests, Personal, Invited Speaker, Educational activities: Pfizer; Financial Interests, Personal, Advisory Board, Non-permanent advisor, Travel accommodation: AstraZeneca; Financial Interests, Personal, Other, Advisory Board: Gilead; Financial Interests, Personal, Other, Advisory Board, Invited speaker: Seagen; Financial Interests, Institutional, Funding, PI for Patricia 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for Prometeo 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for TATEN trial (sponsor: SOLTI Group): MSD; Financial Interests, Institutional, Funding, PI for ATREZZO trial (sponsor: SOLTI Group): Roche; Non-Financial Interests, Member of Board of Directors, Non-profit organization dedicated to breast cancer research: SOLTI Cooperative Group; Non-Financial Interests, Advisory Role, Scientific Evaluator at ISCIII (Spanish Government Academic Research Platform): Instituto de Salud Carlos III. R. Greil: Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Institutional, Stocks/Shares: Novo Nordisk, Lilly; Financial Interests, Personal and Institutional, Funding: Celgene, Roche, Merck, Takeda, AstraZeneca Novartis, Amgen, BMS, MSD, Sandoz, AbbVie Gilead, Daiichi Sankyo; Non-Financial Interests, Other, Travel, Accomodation, Expenses, Consulting, Adv Role: Roche, Amgen, Janssen, AstraZeneca Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo, Sanofi; Other, Travel, Accomodations, Expenses, Consulting, Adv Role., Honoraria: Roche, Amgen, Janssen, AstraZeneca Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo, Sanofi. M.A. Colleoni: Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Leadership Role, CO-Chair Scientific Committee: INTERNATIONAL BREAST CANCER STUDY GROUP. C.M. Kelly: Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Other, Conference attendance/travel expenses: Novartis; Non-Financial Interests, Personal, Other, Steering Committee Member Destiny Breast 11: AstraZeneca. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Writing Engagement, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Writing Engagement, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting SrL; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead, GSK, Eisai, Stemline Menarini; Financial Interests, Personal, Other, Interview: Infomedica srl; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli Lilly, Gilead; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Financial Interests, Institutional, Local PI: Gilead, Seagen; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. R. Spezia: Financial Interests, Personal, Other, Employee and then consultant: Helsinn HHC; Financial Interests, Personal, Other, Consultant: PQE, Eolo; Financial Interests, Personal, Other, Consultant of Fondazione Michelangelo as a consultant of Alira Health: Fondazione Michelangelo; Financial Interests, Personal, Full or part-time Employment: Helsinn HHC; Other, Coinventor of Patent application of elsiglutideNo compensation provided: Helsinn. G. Viale: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, MSD Oncology, Pfizer; Financial Interests, Personal, Other, Consulting fees: Agilent; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Advisory Role: Medscape. All other authors have declared no conflicts of interest.