https://orcid.org/0000-0003-1165-925X
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Abstract
The human epidermal growth factor receptor 2 (HER2)-enriched intrinsic subtype represents up to 75% of all HER2-positive hormone receptor (HR)-negative breast cancer (BC). Optimizing HER2-targeting therapy in this population might allow the omission of anthracycline-based chemotherapy, which is associated with potentially severe toxicities. DECRESCENDO (NCT04675827) is a large, multicenter, single-arm phase II trial in patients with HR-negative, HER2-positive, node-negative early BC evaluating a neoadjuvant pertuzumab and trastuzumab fixed-dose combination administered subcutaneously plus taxane-based chemotherapy followed by adjuvant treatment, adapted according to response to neoadjuvant therapy. The primary end point is the 3-year recurrence-free survival rate in patients with ‘HER2-enriched’ tumors and a pathological complete response. This flexible care substudy offers adjuvant treatment administration outside the hospital to some patients.
Plain language summary
Breast cancer is the most frequent cancer type among women worldwide. Different types of breast cancer exist, defined by the type of proteins on the tumor cell surface:
HER2-positive: overproduction of human epidermal growth factor receptor 2 (HER2);
Hormone receptor-positive: overproduction of the estrogen and/or progesterone hormone receptors.
In the past 30 years, effective anti-HER2 drugs have been developed. However, they are often combined with chemotherapy, which can cause serious side effects (also called toxicities). HER2-positive tumors, which are also hormone receptor-negative, respond better to HER2-targeting drugs with less toxicity than chemotherapy.
The DECRESCENDO trial aims to test treating HER2-positive, hormone receptor-negative patients (with a maximum breast cancer tumor size of 5 cm, without swollen lymph nodes) with pertuzumab + trastuzumab. The combination therapy would be given presurgery to reduce the tumor size as much as possible first (known as neoadjuvant therapy). The intensity of the patient’s chemotherapy would be reduced with only one chemotherapy drug instead of standard three to four drugs. Patients that respond well will require less intense treatment after their surgery. Tissue from the tumors will be tested to see if any of the HER2-positive tumors belong to a subtype known as ‘HER2-enriched’ – this subtype is predicted to be more responsive to the trastuzumab and pertuzumab combination therapy. In a separate study of the DECRESCENDO trial, patients with good responses to neoadjuvant therapy and no safety concerns may continue their postsurgery treatment outside the hospital, such as at home.
Tweetable abstract
The clinical trial DECRESCENDO is currently investigating whether single-agent taxane neoadjuvant chemotherapy in combination with a dual anti-HER2 blockade can be beneficial for certain patients with early HER2-positive HR-negative breast cancerClinical Trial Registration: NCT04675827 and EudraCT 2020-002918-41
Supplementary data
An infographic accompanies this paper. To view or download this infographic in your browser please click here: https://www.futuremedicine.com/doi/suppl/10.2217/fon-2022-1282
Acknowledgments
The authors thank the Clinical Trials Support Unit (CTSU) team of the Institut Jules Bordet, the Breast International Group (BIG), all involved groups and investigators around the world, as well as all the patients and their families. The authors thank Evandro de Azambuja for his helpful suggestions and advice, Florentine Hilbers and Debora Fumagalli for input during early discussions regarding the protocol, and Prudence Francis and Kelly-Anne Phillips for their guidance regarding the ovarian function assessments.
Financial & competing interests disclosure
This study is an investigator-initiated trial supported by a research grant from F. Hoffmann-La Roche Ltd, which is also providing pertuzumab and trastuzumab FDC SC and T-DM1. V Debien: none. V Adam: funding to her institution from F. Hoffmann-La Roche for the conduct of DECRESCENDO and grants to her institution from AstraZeneca, Biovica, GlaxoSmithKline, Novartis, Pfizer, Roche/Genentech, Sanofi and Servier, outside the submitted work. Her institution receives royalties from Agendia for MammaPrint as a result of a collaboration for the conduct of the MINDACT trial. E Coart: none. E Coart: Consultancy fee/honoraria from Eli Lilly, Sandoz and AstraZeneca. Support to attend medical conferences (travel/accommodation/expenses) from Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo (all outside the submitted work). T Goulioti: funding to her institution from F. Hoffmann-La Roche for the conduct of DECRESCENDO and grants to her institution from AstraZeneca, Biovica, GlaxoSmithKline, Novartis, Pfizer, Roche/Genentech, Sanofi and Servier, outside the submitted work. Her institution receives royalties from Agendia for MammaPrint as a result of a collaboration for the conduct of the MINDACT trial. C Molinelli: fees from Novartis and Lilly (outside the submitted work). A Arahmani: funding to her institution from F. Hoffmann-La Roche for the conduct of DECRESCENDO, grants to her institution from AstraZeneca, Biovica, GlaxoSmithKline, Novartis, Pfizer, Roche/Genentech, Sanofi and Servier, outside the submitted work, and royalties to her institution from Agendia for the conduct of Mindact study. G Zoppoli: Travel grants from Novartis, Pfizer and Roche. M Piccart: Research grants to her institute from AstraZeneca, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier and Synthon; board member (scientific board): Oncolytics; consultant (honoraria): AstraZeneca, Camel-IDS/Precirix, Gilead, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Roche-Genentech, Seattle Genetics, Immutep, Seagen, NBE Therapeutics and Frame Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The trial has been or will be submitted for approval to the relevant competent authorities and ethics committees in each participating country before study initiation. All patients are asked to provide written informed consent to participate in DECRESCENDO and patients eligible for the flexible care substudy are also asked to provide specific informed consent for this part of the trial. All study procedures are performed according to the ethical principles of the Declaration of Helsinki and in adherence to the principles of Good Clinical Practice. All personal data are treated in accordance with data protection laws, including the General Data Protection Regulation (GDPR).
Previous presentation
The abstract of the present work was presented at the ASCO Annual Meeting 2022, Chicago, IL, USA [Citation38].