Abstract

Background

Trastuzumab deruxtecan (T-DXd) demonstrated unprecedented efficacy in patients with pretreated HER2+ metastatic breast cancer (mBC). However, few data are available about its efficacy in routine clinical practice. In this multicenter retrospective study, we examined effectiveness and safety of T-DXd in a real-world population.

Methods

Clinico-pathological information about patients with HER2+ mBC who received T-DXd were collected from 12 Italian hospitals. HER2 status was determined locally. Patients who received at least one administration of T-DXd, as any therapy line for advanced disease were included in the analysis. The primary endpoint was real-word PFS (rwPFS).

Results

One hundred and forty-three patients were included. Median age was 66 (range: 37-90), and 4 men were included. Hormone receptor (HR) status was positive in 108 (75%) patients and negative in 35(25%). T-DXd was administered as first, second, third, or subsequent lines in 4 (3%), 16 (11%), 42 (29%), and 81 (57%) patients, respectively. Among 123 patients with measurable disease, the ORR was 68%, and the DCR was 93% (9 CRs, 74 PRs, and 30 SD). Nine (7%) patients had a primary resistance to T-DXd. With a median follow-up of 12 months, the median rwPFS was 16 months. RwPFS was 84%, 59%, and 39% at 6, 12, and 18 months, respectively. A favorable trend in rwPFS was reported in patients receiving T-DXd as I/II line versus further lines (17 vs. 15 months; P = .098). Any-grade toxicity was registered in 84 patients (59%). Most common adverse events (AEs) reported were nausea (33%), neutropenia (21%), and asthenia (21%). Liver toxicity and diarrhea were uncommon (5% and 1%). Severe toxicities was registered in 18% of patients, and the most frequent were neutropenia, nausea/vomiting, and ILD observed in 15, 2, and 3 patients. AEs led to dose reduction in 37 patients (26%). Dose reduction and AEs do not affect patients’ response and survival outcomes.

Conclusions

Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HER2+ mBC. These results are consistent with the results of known findings, and no new safety concerns were reported.

Details

Title
Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study
Author
Botticelli, Andrea 1   VIAFID ORCID Logo  ; Caputo, Roberta 2 ; Scagnoli, Simone 1   VIAFID ORCID Logo  ; Pisegna, Simona 3 ; De Laurentiis, Michelino 2 ; Curigliano, Giuseppe 4   VIAFID ORCID Logo  ; Lambertini, Matteo 5   VIAFID ORCID Logo  ; Pantano, Francesco 6 ; Palazzo, Antonella 7 ; Paris, Ida 8 ; Vernieri, Claudio 9 ; Tedesco, Beatrice 10 ; Giampaglia, Marianna 10 ; Palleschi, Michela 11 ; Ballatore, Zelmira 12 ; Alesini, Daniele 13 ; Giuliana D’Auria 14 ; Fabbri, Agnese 15 ; Rossi, Luigi 16 ; Verrazzo, Annarita 2 ; Scafetta, Roberta 6 ; Marinelli, Daniele 1 ; Sposetti, Caterina 9 ; Barberi, Vittoria 17 ; Strigari, Lidia 18 ; Marchetti, Paolo 19 ; Santini, Daniele 20 ; Fabi, Alessandra 21 

1  Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome , Rome , Italy 
2  Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale , Naples , Italy 
3  Department of Experimental Medicine, Sapienza University of Rome , Rome , Italy 
4  Department of Oncology and Hematology, University of Milan , Milan , Italy 
5  Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova , Genova , Italy 
6  Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico , Rome , Italy 
7  Depatment of Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS , Rome , Italy 
8  Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome , Italy 
9  Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy 
10  Medical Oncology Unit, “S. Carlo” Hospital , Italy 
11  IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” IRST , Meldola , Italy 
12  Clinical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti , Ancona , Italy 
13  UOSD Centro Oncologico S. Spirito e Nuovo Regina Margherita , Ospedale Santo Spirito in Sassia, Rome , Italy 
14  Department of Medical Oncology, Sandro Pertini Hospital , Rome Italy 
15  Department of Oncology and Hematology, Medical Oncology and Breast Unit, Central Hospital of Belcolle , Viterbo , Italy 
16  Multispeciality Department of Oncology, ASL Latina, “Sapienza” University of Rome , Aprilia , Italy 
17  Sapienza Università di Roma - IRCCS Istituto Nazionale Tumori Regina Elena , Rome Italy 
18  Department of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna , Italy 
19  Department of Oncology and Dermatological Oncology, Istituto Dermopatico dell’Immacolata IDI IRCCS , Rome , Italy 
20  Department of Medico-Surgical Sciences and Biotechnology, Polo Pontino, Sapienza University of Rome , Rome , Italy 
21  Precision Medicine in Senology, Scientific Directorate - Department of Women and Child Health, Fondazione Policlinico Universitario “A. Gemelli” IRCCS , Rome , Italy 
Pages
303-310
Publication year
2024
Publication date
Apr 2024
Publisher
Oxford University Press
ISSN
10837159
e-ISSN
1549490X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1093/oncolo/oyad308
ProQuest document ID
3191888771
Copyright
© The Author(s) 2023. Published by Oxford University Press. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.