Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

Autor:	Oliveira M; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Vall d'Hebron University Hospital, and Breast Cancer Group, Vall D'Hebron Institute of Oncology (VHIO), Barcelona. Electronic address: https://twitter.com/MOliveira_MD., Falato C; SOLTI Cancer Research Group, Barcelona; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden., Cejalvo JM; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Hospital Clínico Universitario de Valencia, Valencia., Vila MM; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, ICO - Institut Català d'Oncologia Badalona (Hospital Universitario Germans Trias i Pujol), Badalona., Tolosa P; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Hospital 12 de Octubre, Madrid., Salvador-Bofill FJ; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Hospital Universitario Virgen del Rocio, Sevilla., Cruz J; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife., Arumi M; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Vall d'Hebron University Hospital, and Breast Cancer Group, Vall D'Hebron Institute of Oncology (VHIO), Barcelona., Luna AM; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department; Centro Integral Oncológico Clara Campal HM (CIOCC), Madrid., Guerra JA; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Hospital de Fuenlabrada, Fuenlabrada., Vidal M; SOLTI Cancer Research Group, Barcelona; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clinic de Barcelona, Barcelona., Martínez-Sáez O; SOLTI Cancer Research Group, Barcelona; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clinic de Barcelona, Barcelona., Paré L; SOLTI Cancer Research Group, Barcelona., González-Farré B; SOLTI Cancer Research Group, Barcelona; Pathology Department, Hospital Clinic of Barcelona, Barcelona., Sanfeliu E; SOLTI Cancer Research Group, Barcelona; Pathology Department, Hospital Clinic of Barcelona, Barcelona., Ciruelos E; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Hospital 12 de Octubre, Madrid., Espinosa-Bravo M; SOLTI Cancer Research Group, Barcelona; Breast Cancer Surgical Unit, Vall d'Hebron University Hospital, Barcelona., Pernas S; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Catalan Institute of Oncology - ICO, Breast Cancer Group; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona., Izarzugaza Y; SOLTI Cancer Research Group, Barcelona; Medical Oncology Department, Fundación Jimenez Díaz, Madrid, Spain., Esker S; Research and Development, Daiichi Sankyo, Inc, Basking Ridge, USA., Fan PD; Research and Development, Daiichi Sankyo, Inc, Basking Ridge, USA., Parul P; Research and Development, Daiichi Sankyo, Inc, Basking Ridge, USA., Santhanagopal A; Research and Development, Daiichi Sankyo, Inc, Basking Ridge, USA., Sellami D; Research and Development, Daiichi Sankyo, Inc, Basking Ridge, USA., Villacampa G; SOLTI Cancer Research Group, Barcelona., Ferrero-Cafiero JM; SOLTI Cancer Research Group, Barcelona., Pascual T; SOLTI Cancer Research Group, Barcelona; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clinic de Barcelona, Barcelona., Prat A; SOLTI Cancer Research Group, Barcelona; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clinic de Barcelona, Barcelona. Electronic address: ALPRAT@clinic.cat.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2023 Aug; Vol. 34 (8), pp. 670-680. Date of Electronic Publication: 2023 May 19.
DOI:	10.1016/j.annonc.2023.05.004
Abstrakt:	Background: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  +  1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. Patients and Methods: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. Results: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. Conclusions: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer. (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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