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Evandro de Azambuja, MD, PhD, Comments on the BERENICE Trial


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The invited discussant for the BERENICE trial was Evandro de Azambuja, MD, PhD, Head of the Medical Support Team at the Institut Jules Bordet in Brussels. He concluded from the study that pertuzumab plus trastuzumab, combined with an anthracycline/taxane regimen given every 2 weeks or every 3 weeks, is safe from a cardiac standpoint, based on follow-up out to 5 years.1 Few patients developed New York Heart Association class III or IV heart failure, although some declines in left-ventricular ejection fraction were observed, mostly during the treatment phase rather than over long-term follow-up. “These numbers were small, and the percentage is likely higher than we expected, but [the regimen] is still very ­cardiac-safe,” he commented.

Dr. de Azambuja cited five other trials of combined trastuzu­mab/pertuzumab treatment in early breast cancer: TRYPHAENA, ­APHINITY, KRISTINE, NEOSPHERE, and PEONY (some involve anthracycline-based regimens, and others do not). “All ensure that dual anti-HER2 blockade is not more cardiotoxic than single blockade with trastuzumab,” he commented.

Evandro de Azambuja, MD, PhD

Evandro de Azambuja, MD, PhD

“There were no new safety concerns with longer follow-up of BERENICE, but we don’t have information on patients’ comorbidities or medication use at study entry, and the investigators looked at [left-ventricular ejection fraction] assessment. The question is whether [such] assessment by echocardiography is enough to assess cardiac safety,” he said. Future trials should evaluate patients for earlier, subclinical left-ventricular ejection fraction dysfunction using global longitudinal strain and cardiac biomarkers to predict the onset of toxicity, he advised.

Clinical Efficacy

Regarding the clinical efficacy of the BERENICE regimens, Dr. de Azambuja noted that prognosis was “very good for event-free survival, invasive disease–free survival, and overall survival independent of treatment arm. The 3-year invasive disease–free survival was very similar to the 3-year invasive disease–free survival from APHINITY—94%—so patients did very well in this trial.” APHINITY evaluated 1 year of adjuvant pertuzumab/trastuzumab plus chemotherapy; Dr. de Azambuja was a co-investigator of APHINITY.2

He also remarked that the contribution of the chemotherapy backbone could not be assessed, due to the nonrandomized study design; therefore, one anthracycline schedule could not be shown to be superior to another. “You can’t forget, though, that today we are shifting toward using fewer anthracyclines in patients with HER2-positive early breast cancer,” he added, noting that the study did not include an anthracycline-free backbone. 

DISCLOSURE: Dr. de Azambuja has received honoraria from Roche/Genentech, Seagen, and Zodiac; has served as a consultant or advisor to Libbs, Novartis, Pierre Fabre, and Roche/Genentech; has received institutional research funding from AstraZeneca, GlaxoSmithKline/Novartis, Roche/Genentech, and Servier/Pfizer; and has been reimbursed for travel, accommodations, or other expenses by GlaxoSmithKline and Roche/Genentech.

REFERENCES

1. Dang C, Ewer MS, Delaloge S, et al: Pertuzumab/trastuzumab in early stage HER2-positive breast cancer: 5-year and final analysis of the BERENICE trial. 2021 ESMO Breast Cancer Virtual Congress. Abstract 43O. Presented May 7, 2021. 

2. Piccart M, Procter M, Fumagalli D, et al: Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer in the APHINITY trial: 6 years’ follow-up. J Clin Oncol 39:1448-1457, 2021.

 


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