123O - Randomized phase II trial of neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in early HER2-positive breast cancer (ABCSG-52 / ATHENE)

Background

For most HER2-positive early breast cancer (EBC) patients (pts), neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy is standard of care. To improve the balance between toxicity burden and treatment outcomes, chemotherapy de-escalation has been a major focus in recent years. Among other immunogenic properties, anthracyclines can trigger an immunogenic cell death that engages the adaptive immune system. Within the ABCSG-52 trial we investigated a chemotherapy de-escalation immunotherapy regimen in HER2-positive EBC.

Methods

Pts with previously untreated, histologically confirmed HER2-positive EBC (clinical prognostic stage cT1c-4a-d, N0–3,M0) were randomized 1:1 to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1200mg atezolizumab (TP+A) or TP alone. Afterwards, all pts received 4 cycles of TP+A in combination with epirubicin (part 2). The primary endpoint was pathological complete response (pCR; ypT0/Tis ypN0) in the overall study population. A pCR rate of ≥ 40% was considered as a positive trial result.

Results

Overall, 58 pts were randomized to TP-A (n=29) or TP (n=29) in 9 Austrian study centers. Median age was 57 (range 33-82), 16 pts (27.6%) had hormone-receptor (HR)-negative and 42 (72.4%) had HR-positive tumors. 45 pts (77.6%) had stage ≤ IIA and 13 (22.4%) ≥ IIB. In 35 pts a pCR was observed (60.3%; 95%CI 47.5% - 71.9%), 19 (65.5%) in the TP-A group and 16 (55.2%) in TP group (Δ 10.3%; 95%CI -14.7% - 35.4%). Residual cancer burden (RCB) class 0 or I was seen in 44 out of 55 pts (80%) with valid RCB assessment. Treatment emergent adverse events (AEs) grade ≥ 3 were reported in 17 pts (29.3%), 9 in TP-A group (31.0%) and 8 (27.6%) in TP group. No AEs of special interest (immune-related AEs, cardiac disorders grade ≥ 2, or infusion-related reactions) grade ≥ 3 were detected. Outcome according to PD-L1 expression status is currently analyzed and will also be presented at the meeting.

Conclusions

For HER2-positive EBC, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab and epirubicin is highly effective and safe and merits further investigation.

Clinical trial identification

EudraCT 2019-002364-27.

Legal entity responsible for the study

Austrian Breast and Colorectal Cancer Study Group (ABCSG).

Funding

Academic group WITH funding from a pharma: Austrian Breast and Colorectal Cancer Study Group (ABCSG); Provision of IMP and financial support by Roche Austria GmbH.

Disclosure

G. Rinnerthaler: Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Eli Lilly, Gilead, Novartis, Pfizer, Roche, Seagen; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Merck, MSD, Novartis, Pfizer, Pierre Fabre, Roche; Financial Interests, Personal, Other, Travel grant: Amgen, Daiichi Sankyo, Eli Lilly, Gilead, Merck, Pfizer, Roche; Non-Financial Interests, Member: Austrian Society for Haematology and Medical Oncology (OeGHO). D. Egle: Financial Interests, Personal, Advisory Board: AstraZeneca, Gilead, Pfizer, Novartis, Lilly, Seagen, Pierre-Fabre, MSD; Financial Interests, Personal, Invited Speaker: Roche, Sirius Medical; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo. R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca, Seagen, Roche, Novartis, Eli Lilly, Pierre-Fabre, Daiichi, Gilead, MSD, Pfizer, Eisai, Gruenenthal; Financial Interests, Personal, Advisory Board: Daiichi, AstraZeneca, Roche, Novartis, Eli Lilly, Pierre-Fabre, MSD, Gilead, Seagen, Eisai, Gruenenthal; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. A.L. Petzer: Financial Interests, Personal, Advisory Board: Novartis, Amgen, Celgene-BMS, Daiichi Sankyo, AstraZeneca, Seagen, Roche, Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo. M. Balic: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, MSD, Pierre Fabre, Pfizer, Roche, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eli Lilly, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Gilead; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker, Steering Committee Member, Coordinating PI, Advisory role: Roche; Financial Interests, Institutional, Invited Speaker: Roche, Austrian Breast and Colorectal Cancer Study Group, MSD, Qiagen, Amgen, Pierre Fabre, Novartis, Pfizer, Gilead. E. Petru: Financial Interests, Personal, Advisory Board, Attendance fees: AstraZeneca, Eisai, Lilly, GSK; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, EISAI, Lilly, GSK; Financial Interests, Personal, Advisory Board, Fees: MSD, Novartis, Pharma Mar, Roche, Seagen, Pierre Fabre, Daiichi Sankyo, Gilead; Financial Interests, Personal, Invited Speaker, Fees: MSD, Novartis, Roche, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker, Fees to institution: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Patient Fees: Roche; Financial Interests, Institutional, Invited Speaker, Fees: Lilly, GSK, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Fees: Seagen, Pierre Fabre. C.F. Singer: Financial Interests, Personal, Other, consultancy: Amgen; Financial Interests, Personal, Advisory Board, Advisory Function: Novartis; Financial Interests, Personal, Advisory Board, Advisory Role: Roche; Financial Interests, Personal, Other, Study Support: Pfizer; Financial Interests, Personal, Advisory Board, Advisory, Speaker Honoraria, Study Support: AstraZeneca; Financial Interests, Personal, Invited Speaker, Study Coordinator: Amgen; Non-Financial Interests, Principal Investigator, Study: Amgen, AstraZeneca; Non-Financial Interests, Project Lead, Register: Pfizer. V. Bjelic-Radisic: Non-Financial Interests, Principal Investigator, PI of the EORTC Follow Up 16-17 study PI of EORTC QLQ BR Update study: EORTC. S.P. Gampenrieder: Financial Interests, Personal, Invited Speaker: Novartis, BMS, AstraZeneca, Pfizer, Lilly, Seagen, Daichi Sankyo, Janssen; Financial Interests, Personal, Advisory Board: Novartis, Lilly, AstraZeneca, MSD, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Funding: Roche; Other, Travel grant: Roche, Novartis, Pfizer, Celgene, Daiichi Sankyo, Janssen. Z.A. Bago-Horvath: Financial Interests, Personal, Advisory Board, Advisory Board Trastuzumab Deruxtecan: AstraZeneca, Daichi Sanyo; Financial Interests, Personal, Advisory Board, Advisory Board Sacituzumab Govitecan: Gilead; Financial Interests, Personal, Other, Travel support: Roche; Financial Interests, Personal, Invited Speaker, Speaker at CME Lectures: MSD; Non-Financial Interests, Institutional, Product Samples, Reagents: Roche. M. Filipits: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Eli Lilly, Biorad, Merck, Novartis. M.I. Gnant: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Novartis, Pierre Fabre; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Eli Lilly, Menarini-Stemline; Financial Interests, Personal, Expert Testimony: Veracyte; Financial Interests, Invited Speaker: Pfizer; Other, Spouse is employed by Sandoz: Sandoz. R. Greil: Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Personal and Institutional, Funding: Celgene, Roche, Merck, Takeda, AstraZeneca Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo. All other authors have declared no conflicts of interest.