Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study.

DE-REAL study HER2+ breast cancer trastuzumab deruxtecan

Journal

The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837

Informations de publication

Date de publication:
23 Nov 2023
Historique:
received: 26 07 2023
accepted: 09 10 2023
medline: 23 11 2023
pubmed: 23 11 2023
entrez: 23 11 2023
Statut: aheadofprint

Résumé

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. 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). 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

DOI: 10.1093/oncolo/oyad308 PMID: 37995313
pubmed: 37995313
pii: 7444338
doi: 10.1093/oncolo/oyad308
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press.

Auteurs

Andrea Botticelli (A)

Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, Rome, Italy.
ORCID: 0000-0002-6425-9893

Roberta Caputo (R)

Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, Italy.

Simone Scagnoli (S)

Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, Rome, Italy.
ORCID: 0000-0003-4943-5622

Simona Pisegna (S)

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Michelino De Laurentiis (M)

Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, Italy.

Giuseppe Curigliano (G)

Department of Oncology and Hematology, University of Milan, Milan, Italy.
Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy.
ORCID: 0000-0003-1781-2518

Matteo Lambertini (M)

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.
Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
ORCID: 0000-0003-1797-5296

Francesco Pantano (F)

Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.

Antonella Palazzo (A)

Depatment of Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.

Ida Paris (I)

Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Claudio Vernieri (C)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy.

Beatrice Tedesco (B)

Medical Oncology Unit, "S. Carlo" Hospital, Italy.

Marianna Giampaglia (M)

Medical Oncology Unit, "S. Carlo" Hospital, Italy.

Michela Palleschi (M)

IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRST, Meldola, Italy.

Zelmira Ballatore (Z)

Clinical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti, Ancona, Italy.

Daniele Alesini (D)

UOSD Centro Oncologico S. Spirito e Nuovo Regina Margherita, Ospedale Santo Spirito in Sassia, Rome, Italy.

Giuliana D'Auria (G)

Department of Medical Oncology, Sandro Pertini Hospital, Rome Italy.

Agnese Fabbri (A)

Department of Oncology and Hematology, Medical Oncology and Breast Unit, Central Hospital of Belcolle, Viterbo, Italy.

Luigi Rossi (L)

Multispeciality Department of Oncology, ASL Latina, "Sapienza" University of Rome, Aprilia, Italy.

Annarita Verrazzo (A)

Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, Italy.

Roberta Scafetta (R)

Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.

Daniele Marinelli (D)

Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, Rome, Italy.

Caterina Sposetti (C)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Vittoria Barberi (V)

Sapienza Università di Roma - IRCCS Istituto Nazionale Tumori Regina Elena, Rome Italy.

Lidia Strigari (L)

Department of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Paolo Marchetti (P)

Department of Oncology and Dermatological Oncology, Istituto Dermopatico dell'Immacolata IDI IRCCS, Rome, Italy.

Daniele Santini (D)

Department of Medico-Surgical Sciences and Biotechnology, Polo Pontino, Sapienza University of Rome, Rome, Italy.
Medical Oncology A, AOU Policlinico Umberto I, Rome, Italy.

Alessandra Fabi (A)

Precision Medicine in Senology, Scientific Directorate - Department of Women and Child Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Classifications MeSH