Patritumab deruxtecan in HR+HER2− advanced breast cancer: a phase 2 trial

Antibody-drug conjugates have shown impressive clinical outcomes, particularly in metastatic breast cancer, but biomarkers to predict response and resistance remain unidentified. Here we report the results of ICARUS-BREAST01, a phase 2 study evaluating efficacy, safety and biomarkers of response and resistance to patritumab deruxtecan (HER3-DXd), in patients with HR<sup>+</sup>HER2<sup>-</sup> metastatic breast cancer, who previously progressed on CDK4/6 inhibitors and one line of chemotherapy. From May 2021 to June 2023, 99 patients were enrolled to receive HER3-DXd 5.6 mg kg<sup>-1</sup> intravenously every 3 weeks. The study met its primary endpoint, showing an overall response rate of 53.5% (90% confidence interval [44.8-62.1%]). The most frequent adverse events were fatigue (83%), nausea (75%), diarrhea (53%) and alopecia (40%). Exploratory biomarker analysis of baseline tumor samples suggested preliminary associations between overall response rate and both HER3 spatial distribution and absence of estrogen receptor 1 (ESR1) mutations, as well as between progression-free survival and HER3 expression, pending further validation. Analysis of on-treatment tumor samples showed that treatment efficacy seems to be associated with antibody-drug conjugate intratumoral distribution and interferon response. Overall, HER3-DXd showed promising activity and manageable tolerability in patients with HR<sup>+</sup>HER2<sup>-</sup> metastatic breast cancer who progressed on CDK4/6 inhibitors. These findings highlight the need for larger trials to define HER3-DXd efficacy relative to other drugs, including antibody-drug conjugates (ClinicalTrials.gov Identifier: NCT04965766 ).

Authors

Institutions

Publication Details

Journal
Nature Medicine
Published
2025-09-04
DOI
https://doi.org/10.1038/s41591-025-03885-3
Citations
5
Primary Topic
Advanced Breast Cancer Therapies
Type
article
Field-Weighted Citation Impact
7.59

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Patritumab deruxtecan in HR+HER2− advanced breast cancer: a phase 2 trial

Patricia Kannouche, Fabrice André, Hugues Talbot, Barbara Pistilli et al.
5 citations
Nature Medicine
Advanced Breast Cancer Therapies
7.59
article

Patritumab deruxtecan in HR+HER2− advanced breast cancer: a phase 2 trial

Patricia Kannouche, Fabrice André, Hugues Talbot, Barbara Pistilli, Loïc Le Bescond, Magali Lacroix‐Triki, Yves Akoli Koudou, Lie Li, Diep Thi Ngoc Tran, David Sternberg, Livia Pierotti, Elsa Bernard, P. Le Guyader, Véronique D’Hondt, Marianne Oulhen, Nicolas Signolle, Françoise Farace, Jean‐Sébastien Frenel, Thomas Bachelot, Noémie Corcos, Jacqueline Deneuve, Alexia Alfaro, Agnès Ducoulombier, Élise Deluche, M.F. Mosele, Florence Dalenc, Fumitaka Suto, Didier Mayeur, Fathia Mami‐Chouaib, Karine Godefroy, Stefan Michiels, Cyril Catelain, Bastien Job, Stergios Christodoulidis, Dalila Sellami, Cécile Vicier, Marc Antoine Benderra, Yoann Pradat, Andrea Sporchia, Nathalie Droin, Ghada Nachabeh, Séverine Badel, Rasha Cheikh-Hussin, Guillaume Montagnac, Maria Vakalopoulou, Delphine Loirat
article en
5 citations

Abstract

Antibody-drug conjugates have shown impressive clinical outcomes, particularly in metastatic breast cancer, but biomarkers to predict response and resistance remain unidentified. Here we report the results of ICARUS-BREAST01, a phase 2 study evaluating efficacy, safety and biomarkers of response and resistance to patritumab deruxtecan (HER3-DXd), in patients with HR<sup>+</sup>HER2<sup>-</sup> metastatic breast cancer, who previously progressed on CDK4/6 inhibitors and one line of chemotherapy. From May 2021 to June 2023, 99 patients were enrolled to receive HER3-DXd 5.6 mg kg<sup>-1</sup> intravenously every 3 weeks. The study met its primary endpoint, showing an overall response rate of 53.5% (90% confidence interval [44.8-62.1%]). The most frequent adverse events were fatigue (83%), nausea (75%), diarrhea (53%) and alopecia (40%). Exploratory biomarker analysis of baseline tumor samples suggested preliminary associations between overall response rate and both HER3 spatial distribution and absence of estrogen receptor 1 (ESR1) mutations, as well as between progression-free survival and HER3 expression, pending further validation. Analysis of on-treatment tumor samples showed that treatment efficacy seems to be associated with antibody-drug conjugate intratumoral distribution and interferon response. Overall, HER3-DXd showed promising activity and manageable tolerability in patients with HR<sup>+</sup>HER2<sup>-</sup> metastatic breast cancer who progressed on CDK4/6 inhibitors. These findings highlight the need for larger trials to define HER3-DXd efficacy relative to other drugs, including antibody-drug conjugates (ClinicalTrials.gov Identifier: NCT04965766 ).

Nature MedicineVol. 31(10)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris-Saclay (FR), Institut Gustave Roussy (FR), Sorbonne Université (FR), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers (FR), Centre Georges François Leclerc (FR), Assistance Publique – Hôpitaux de Paris (FR), Centre Léon Bérard (FR), Institut de Cancérologie de l'Ouest (FR), CentraleSupélec (FR), Centre Hospitalier Universitaire de Limoges (FR), Institut Claudius Regaud (FR), Institut de Recherche en Cancérologie de Montpellier (FR), Hôpital Universitaire Dupuytren (FR), Institut Paoli-Calmettes (FR), Centre Antoine Lacassagne (FR), Daiichi Sankyo (United States) (US), Hôpital Tenon (FR), Institut Regional du Cancer de Montpellier (FR), Institut Curie (FR)
Eli Lilly and Company, Pfizer, AstraZeneca, Yuhan, Seagen, Agence Nationale de la Recherche, Eisai, Servier, Daiichi Sankyo Europe
Openalex Percentile: Top 2%
Advanced Breast Cancer Therapies
7.59
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.