Background

BERENICE was designed to establish the cardiac safety of neoadjuvant pertuzumab/trastuzumab (PH) with anthracycline-containing chemotherapies (primary objective). Here we report the 5-year outcomes at end-of-study (clinical cut-off date: 25/08/2020), including additional safety and efficacy data (secondary objectives).

Methods

BERENICE was a multicenter, open-label, non-comparative phase II trial. Patients with stage IIA to III HER2-positive breast cancer and a left ventricular ejection fraction (LVEF) ≥55% were allocated per physician's choice to cohort A (dose-dense doxorubicin/cyclophosphamide every 2 weeks [q2w] x 4 → paclitaxel q1w x 12) or cohort B (5-fluorouracil, epirubicin, cyclophosphamide q3w x 4 → docetaxel q3w x 4). PH q3w was initiated from the start of taxanes and continued after surgery for a total of 17 cycles.

Results

Intention-to-treat population comprised 199 patients in cohort A and 201 in cohort B, with a median follow-up of 64.5 months. No new cardiac safety issues were seen, with few events occurring in the treatment-free period and a low incidence of class III/IV congestive heart failure (Table). Event-free survival (EFS) rates at 5 years were 90.8% (95% CI, 86.5-95.2) and 89.2% (84.8-93.6) in cohorts A and B, respectively. Overall survival rates at 5 years were 96.1% (93.3-98.9) and 93.8% (90.3-97.2) in cohorts A and B, respectively. According to PAM50 classification, available for 339 patients, most patients had HER2-enriched tumors (51.6%), with 5-year EFS rates of 93.1% (87.2-98.9) in cohort A and 88.3% (81.8-94.8) in cohort B Table: 43O

Conclusions

The final analysis of BERENICE showed sustained cardiac safety and favorable long-term efficacy outcomes, further supporting neoadjuvant/adjuvant PH with standard anthracycline-containing therapies in patients with early stage HER2-positive breast cancer.

Clinical trial identification

NCT02132949 (WO29217), 25 January 2014.

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by Alison McGonagle, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

C. Dang: Honoraria (self): F. Hoffmann-La Roche Ltd., Genentech Inc., Daiichi Sankyo, Lilly, Puma Biotechnology; Advisory/Consultancy: F. Hoffmann-La Roche Ltd., Genentech Inc., Daiichi Sankyo, Lilly, Puma Biotechnology; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. M.S. Ewer: Advisory/Consultancy: AstraZeneca, Bayer, Boehringer Ingelheim; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions.: Roche. S. Delaloge: Advisory/Consultancy: AstraZeneca, Pierre Fabre, BMS, Roche, Lilly, Novartis, Pfizer, Servier, Orion, Puma, Sanofi, Cellectis; Research grant/Funding (institution): AstraZeneca, Roche, GE, Pfizer, Puma, Sanofi, BMS, MSD; Travel/Accommodation/Expenses: Pfizer, Roche, AstraZeneca; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. J-M. Ferrero: Honoraria (self): Pfizer, Lilly, Novartis; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. R. Colomer: Advisory/Consultancy: Roche, Lilly, MSD, AstraZeneca; Research grant/Funding (self): Roche, Lilly, MSD, BMS; Travel/Accommodation/Expenses: Roche, MSD; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. L. de la Cruz Merino: Advisory/Consultancy: MSD, Roche, Celgene; Speaker Bureau/Expert testimony: MSD, Roche, BMS, Amgen; Research grant/Funding (institution): BMS, Roche; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. K. Dadswell: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Roche; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. M. Verrill: Honoraria (self): Roche, Lilly, Pfizer, Novartis, Exact Sciences; Research grant/Funding (institution): Roche, Pfizer, Amgen, Novartis; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. D. Eiger: Research grant/Funding (self): Novartis; Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Roche; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. S. Sarkar: Full/Part-time employment, Roche external business partner: PAREXEL; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. S. de Haas: Full/Part-time employment: Roche; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. E. Restuccia: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Roche; Non-remunerated activity/ies, Third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. S.M. Swain: Honoraria (self): AstraZeneca, Daiichi Sankyo, Roche/Genentech, Exact Sciences (Genomic Health), Molecular Templates, Silverback Therapeutics, Tocagen, Lilly, Natera, Athenex, Bejing Medical Foundation; Advisory/Consultancy: AstraZeneca, Daiichi Sankyo, Roche/Genentech, Exact Sciences (Genomic Health), Molecular Templates, Silverback Therapeutics, Tocagen, Lilly, Natera, Athenex, Bejing Medical Foundation; Advisory/Consultancy, Scientific advisory board: Inivata; Research grant/Funding (institution): Roche/Genentech, Kailos Genetics; Travel/Accommodation/Expenses: BMS, Lilly, Roche/Genentech, Daiichi Sankyo, Caris Life Sciences; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche.

Background

One of the key potential benefits of NAC is to sterilise the axilla of patients who present with axillary stage positive disease. In certain patients, this allows axillary conservation as opposed to an axillary clearance (ANC). This unit’s standard practice was to offer TAD to patients with node positive disease with favourable biology following NAC if a radiological response had been seen. This prospective study considers the impact of this approach to the management of these patients in a real-world setting.

Methods

Prospective data collection from a large breast screening institution of all patients undergoing NAC with axillary node positive disease (1-2 nodes or 3+ nodes) from May 2014 to January 2021. Axillary pCR is defined as no tumour cells seen in nodes.

Results

A total 99 patients, with node positive disease, were treated with NAC in this time-period. The overall axillary pCR rate in the population was 49.5%. In patients with 1-2 nodes, the pCR rate was 56.3% compared with 43.1% in a higher axillary burden; breakdown of these figures as stratified by hormone receptor status is illustrated in the table. TAD was performed successfully in 70.4% patients with 1-2 nodes without the need for an ANC. Of the 22 patients who had 3+ nodes at presentation with a pCR, 72.7% (16) underwent an ANC who may have avoided this if they had been considered for a TAD. Table: 69P

pCR rate stratified by axillary burden and hormone receptor status

Conclusions

Pathological response rates in this study are relatively consistent with those published in recent major trials. Evolution of the practice in this unit now includes offering patients presenting with 3+ nodes, favourable biology and a radiological response, a TAD rather than a potentially unnecessary ANC following appropriate counselling.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Verrill: Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): Novartis; Research grant/Funding (self): Amgen; Honoraria (self): Lilly; Honoraria (self): Exact Science. N. Cresti: Advisory/Consultancy, Research grant/Funding (institution): Roche. H. Cain: Advisory/Consultancy: Roche; Advisory/Consultancy: AZ; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Exact Science. All other authors have declared no conflicts of interest.