Adding Checkpoint Inhibition to Anti-HER2 Breast Cancer Therapy Brings no Benefit [ESMO Virtual Plenary Press Release]

VP6-2021 – IMpassion050: A phase III study of neoadjuvant atezolizumab + pertuzumab + trastuzumab + chemotherapy (neoadj A + PH + CT) in high-risk, HER2-positive early breast cancer (EBC)

J. Huober1, C.H. Barrios2, N. Niikura3, M. Jarzab4, Y-C. Chang5, S.L. Huggins-Puhalla6, V. Graupner7, D. Eiger7, V. Henschel8, N. Gochitashvili9, C. Lambertini10, E. Restuccia7, H. Zhang11
1Cantonal Hospital, Breast Center St. Gallen, St. Gallen, Switzerland, 2Centro de Pesquisa em Oncologia, Hospital São Lucas, PUCRS, Porto Alegre, Brazil, 3Department of Breast Oncology, Tokai University School of Medicine, Tokai, Japan, 4Breast Cancer Unit, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland, 5Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan, 6Magee-Women’s Hospital, University of Pittsburgh, Pittsburgh, PA, USA, 7Product Development Oncology, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 8Biostatistics, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 9Product Development Safety, Roche Products Limited, Welwyn Garden City, UK, 10Oncology Biomarker Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 11Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Background: PH + CT is standard of care for high-risk, HER2-positive EBC. PH activates antibody-dependent cellular cytotoxicity; combining A + PH + CT may restore anti-cancer immunity and further enhance activity. IMpassion050 (NCT03726879), a double-blind, randomised, placebo (PL)-controlled study, evaluated efficacy and safety of neoadj A/PL + PH + CT. We report the primary analysis.

Methods: Patients (pts) had T2–4, N1–3, M0 disease. HER2-positivity, PD-L1 and hormone receptor (HR) status were assessed centrally. Stratification factors: T stage, HR and PD-L1 status. Randomisation was 1:1 to A/PL 840 mg q2w Cycles (C) 1–4/1200 mg q3w C5–8 + dose-dense doxorubicin + cyclophosphamide (ddAC) q2w C1–4 followed by paclitaxel (Pac) qw C5–8 + standard PH q3w C5–8. Post-surgery, pts continued PH + A/PL to complete 52 weeks in total. Pts with residual disease could switch to trastuzumab emtansine + A/PL. Co-primary endpoints: Pathological complete response (pCR; ypT0/is ypN0) in the ITT and PD-L1-positive populations. Safety was a secondary endpoint. On 26/01/21 the IDMC met and recommended that A/PL treatment (Tx) be stopped due to an unfavourable benefit–risk profile. Data were analysed early (clinical cutoff: 05/02/21), with 3 pts yet to undergo surgery.

Results: 226 pts were assigned to A; 228 to PL. pCR in the ITT population of the A and PL arms: 62.4% (95% CI 55.7, 68.7) and 62.7% (56.1, 69.0), respectively (Δ –0.33%; –9.2, 8.6; P = 1.0). pCR in the PD-L1-positive population (109 per arm): 64.2% (54.5, 73.2) and 72.5% (63.1, 80.6), respectively (Δ –8.26%; –20.6, 4.0; P = 0.2). In the neoadj phase, Grade 3/4 adverse events (AEs; 51.8% v 43.6%) and serious AEs (19.5% v 13.3%) were increased with A without increased withdrawals from any study Tx. There were 4 Grade 5 AEs in the neoadj phase (alveolitis,* septic shock,* sepsis, COVID-19 [*Tx-related, per investigator]) and 1 in the adjuvant phase (COVID-19); all with A and confounded by comorbidities and concurrent events.

Conclusions: A + ddAC-PacPH did not result in increased pCR in the ITT or PD-L1-positive populations. Overall, the safety profile was consistent with the known profile in other combination studies with A, with no new safety signals.

Clinical trial identification: NCT03726879 (BO40747), 1 Nov 2018

Editorial acknowledgement: Support for third-party writing assistance for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd

Legal entity responsible for the study: F. Hoffmann-La Roche Ltd, Basel, Switzerland

Funding: F. Hoffmann-La Roche Ltd, Basel, Switzerland

Disclosure: J. Huober: Financial Interests, Personal, Invited Speaker, Honoraria: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Eisai, AbbVie; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Study funding: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Board: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, AbbVie; Financial Interests, Institutional, Research Grant: Celgene, Novartis, Hexal; Financial Interests, Personal, Other, Travel expenses: Roche, Pfizer, Novartis, Celgene, Daiichi.
C.H. Barrios: Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Study funding: F. Hoffmann-La Roche Ltd.
N. Niikura: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Eisai, Chugai, Daiichi Sankyo; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Study funding: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Board: Roche, Pfizer, AstraZeneca, MSD, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Chugai, Daiichi-Sankyo, Pfizer, Eisai.
M. Jarzab: Financial Interests, Personal, Invited Speaker: F. Hoffmann-La Roche Ltd; Pfizer; Novartis, MSDr; Non-Financial Interests, Personal, Research Grant, Third-party writing support : F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Study funding: F. Hoffmann-La Roche Ltd.
Y. Chang: Financial Interests, Institutional, Research Grant, Study funding: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd.
S.L. Huggins-Puhalla: Financial Interests, Institutional, Research Grant, Study funding: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant: Pfizer, AstraZeneca; Non-Financial Interests, Personal, Other, Consultant/Steering Committee membership: AbbVie, Roche.
V. Graupner: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd.
D. Eiger: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Research Grant, ESMO Fellowship 2018–2019: Novartis.
V. Henschel: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd.
N. Gochitashvili: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd.
C. Lambertini: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd.
E. Restuccia: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd.
H. Zhang: Financial Interests, Institutional, Research Grant, Study funding: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third-party writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Consultant on clinical trials: Roche/Genentech.

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