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

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. Zhang^11
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.