R. Colomer (Madrid, Spain)

Hospital Universitario La Princesa

Author Of 1 Presentation

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Best abstracts Proffered paper

43O - Pertuzumab/Trastuzumab in Early Stage HER2-positive Breast Cancer: 5-year and Final Analysis of the BERENICE Trial (ID 235)

Presentation Number
43O
Lecture Time
17:40 - 17:52
Speakers
Session Name
Best abstracts
Room
Channel 1
Date
Fri, 07.05.2021
Time
17:15 - 18:30

Abstract

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

Safety population Cohort A (N=199) Cohort B (N=198)*
No. of patients with at least one LVEF decrease to ≥10% points from baseline to an LVEF <50% (whole study) No. during the treatment-free follow-up period 27 (13.6%) 12 (6.0%) 24 (12.1%)7 (3.5%)
No. of patients with New York Heart Association class III/IV congestive heart failure (whole study)No. during the treatment-free follow-up period 3 (1.5%)0 2 (1.0%)1 (0.5%)

*3 patients without safety data available

 .

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.

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Author Of 1 Presentation

 On-Demand ePoster Display

46P - Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) plus chemotherapy in HER2-positive early breast cancer (EBC): Safety results from the adjuvant phase of the randomised, open-label, multicentre phase 3 (neo)adjuvant FeDeriCa study

Abstract

Background

In the primary analysis of the neoadjuvant phase of the FeDeriCa study (NCT03493854; Tan AR, et al. Lancet Oncol 2021), PH FDC SC cycle 7 P + H serum trough concentrations were non-inferior to intravenous (IV) P + H, with comparable total pathological complete response rates and safety profiles. We present updated descriptive safety data that span the adjuvant phase of the study, with an additional 12 months beyond the primary analysis.

Methods

Patients (pts) with HER2-positive operable, locally advanced or inflammatory stage II–IIIC BC and left ventricular ejection fraction (LVEF) ≥55% were randomised 1:1 to eight neoadjuvant chemotherapy cycles (investigator’s choice between two standard regimens) + P IV (loading dose 840 mg, maintenance 420 mg) + H IV (8 mg/kg → 6 mg/kg) or chemotherapy + PH FDC SC (1200 mg P/600 mg H → 600 mg each as FDC SC) every 3 weeks during cycles 5–8. After surgery, pts continued adjuvant HER2-targeted treatment only, as randomised, to complete 18 cycles. Safety was assessed by NCI-CTCAE v4.

Results

Clinical cut-off was 10 July 2020. Adverse events (AEs) are shown in the table; the most common were diarrhoea, radiation skin injury and arthralgia. Infusion-/administration-related reactions within 24 hours were higher with PH FDC SC (17%) than with P + H IV (5%), all grade 1/2 and mostly due to local injection site reactions. No grade ≥3 anaphylaxis/hypersensitivity was reported in either arm.

AEs; % of pts with ≥1: P + H IV (n = 252) PH FDC SC (n = 248)
Any 87% 89%
Grade ≥3 15% 11%
Serious 3% 4%
To monitor 46% 45%
Leading to death <1%* 0
Cardiac
Primary† 1% 2%
Secondary 4% 1%

Safety population *Related cardiac failure †Clinically significant LVEF drops: 1% of pts per arm.

Conclusions

Overall safety and tolerability, including cardiac safety, of PH FDC SC in the adjuvant phase of FeDeriCa remained comparable to P + H IV, with the exception of AEs associated with the different routes of administration. Results are in line with the expectation that most AEs with PH FDC SC or P + H IV are observed during concomitant chemotherapy.

Clinical trial identification

NCT03493854 (WO40324), 2 Feb 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

S-A. Im: Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Hanmi, GSK, Lilly, MSD, Novartis, Roche, Pfizer; Research grant/Funding (institution), Investigator-initiated clinical trial research grant through institution: AstraZeneca, Eisai, Daewoong Pharm, Roche, Pfizer; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A.R. Tan: Honoraria (self): Genentech, Novartis, Immunomedics, Celgene, AbbVie, Athenex, G1 Therapeutics, Eisai, Merck; Research grant/Funding (institution), Institutional clinical trial support: Roche/Genentech, Pfizer, Merck, Tesaro; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Mattar: Advisory/Consultancy, Advisory board consultant: Roche, Novartis, Pierre Fabre, AstraZeneca, Exact sciences; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. R. Colomer: Honoraria (self): Roche, Eli Lilly, MSD, AstraZeneca; Research grant/Funding (institution): Roche, Lilly, MSD, BMS, AstraZeneca, Pfizer, Novartis; Non-remunerated activity/ies: Roche, MSD; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. D. Stroyakovskii: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. Z. Nowecki: Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. De Laurentiis: Honoraria (self), Speaker’s honoraria and advisory board honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Advisory/Consultancy: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. J-Y. Pierga: Honoraria (self): Roche, AstraZeneca, Pfizer, Amgen, Novartis, Exact Sciences, Seagen, Lilly, Pierre Fabre, MSD; Honoraria (institution): BMS, Roche, MSD, Eisai, Novartis, Sanofi; Speaker Bureau/Expert testimony: Daiichi Sankyo; Research grant/Funding (institution): Servier, Roche, Menarini Silicon Biosystems; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. K.H. Jung: Honoraria (self), Advisory board honoraria: Roche, Novartis, AstraZeneca, Takeda, Celgene; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Schem: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Aguila: Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. T. Badovinac Crnjevic: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. S. Heeson: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. Shivhare: Shareholder/Stockholder/Stock options: Roche Products Limited; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Alexandrou: Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. E. Restuccia: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Jackisch: Honoraria (self): AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Advisory/Consultancy: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Research grant/Funding (institution): Roche, Exact Sciences; Travel/Accommodation/Expenses: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche.

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