PMID- 37995313
OWN - NLM
STAT- MEDLINE
DCOM- 20240408
LR  - 20240408
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 29
IP  - 4
DP  - 2024 Apr 4
TI  - Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic 
      Breast Cancer: The DE-REAL Study.
PG  - 303-310
LID - 10.1093/oncolo/oyad308 [doi]
AB  - 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.
CI  - (c) The Author(s) 2023. Published by Oxford University Press.
FAU - Botticelli, Andrea
AU  - Botticelli A
AUID- ORCID: 0000-0002-6425-9893
AD  - Department of Radiological, Oncological and Pathological Science, Sapienza 
      University of Rome, Rome, Italy.
FAU - Caputo, Roberta
AU  - Caputo R
AD  - Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, 
      Italy.
FAU - Scagnoli, Simone
AU  - Scagnoli S
AUID- ORCID: 0000-0003-4943-5622
AD  - Department of Radiological, Oncological and Pathological Science, Sapienza 
      University of Rome, Rome, Italy.
FAU - Pisegna, Simona
AU  - Pisegna S
AD  - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
FAU - De Laurentiis, Michelino
AU  - De Laurentiis M
AD  - Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, 
      Italy.
FAU - Curigliano, Giuseppe
AU  - Curigliano G
AUID- ORCID: 0000-0003-1781-2518
AD  - Department of Oncology and Hematology, University of Milan, Milan, Italy.
AD  - Division of New Drugs and Early Drug Development for Innovative Therapies, 
      European Institute of Oncology, IRCCS, Milan, Italy.
FAU - Lambertini, Matteo
AU  - Lambertini M
AUID- ORCID: 0000-0003-1797-5296
AD  - Department of Internal Medicine and Medical Specialties (DiMI), School of 
      Medicine, University of Genova, Genova, Italy.
AD  - Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale 
      Policlinico San Martino, Genova, Italy.
FAU - Pantano, Francesco
AU  - Pantano F
AD  - Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, 
      Italy.
FAU - Palazzo, Antonella
AU  - Palazzo A
AD  - Depatment of Medical Oncology, Comprehensive Cancer Center, Fondazione 
      Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
FAU - Paris, Ida
AU  - Paris I
AD  - Department of Woman and Child Health, Fondazione Policlinico Universitario A. 
      Gemelli IRCCS, Rome, Italy.
FAU - Vernieri, Claudio
AU  - Vernieri C
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 
      Milan, Italy.
AD  - IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy.
FAU - Tedesco, Beatrice
AU  - Tedesco B
AD  - Medical Oncology Unit, "S. Carlo" Hospital, Italy.
FAU - Giampaglia, Marianna
AU  - Giampaglia M
AD  - Medical Oncology Unit, "S. Carlo" Hospital, Italy.
FAU - Palleschi, Michela
AU  - Palleschi M
AD  - IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRST, Meldola, 
      Italy.
FAU - Ballatore, Zelmira
AU  - Ballatore Z
AD  - Clinical Oncology, Universita Politecnica delle Marche, AOU Ospedali Riuniti, 
      Ancona, Italy.
FAU - Alesini, Daniele
AU  - Alesini D
AD  - UOSD Centro Oncologico S. Spirito e Nuovo Regina Margherita, Ospedale Santo 
      Spirito in Sassia, Rome, Italy.
FAU - D'Auria, Giuliana
AU  - D'Auria G
AD  - Department of Medical Oncology, Sandro Pertini Hospital, RomeItaly.
FAU - Fabbri, Agnese
AU  - Fabbri A
AD  - Department of Oncology and Hematology, Medical Oncology and Breast Unit, Central 
      Hospital of Belcolle, Viterbo, Italy.
FAU - Rossi, Luigi
AU  - Rossi L
AD  - Multispeciality Department of Oncology, ASL Latina, "Sapienza" University of 
      Rome, Aprilia, Italy.
FAU - Verrazzo, Annarita
AU  - Verrazzo A
AD  - Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, 
      Italy.
FAU - Scafetta, Roberta
AU  - Scafetta R
AD  - Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, 
      Italy.
FAU - Marinelli, Daniele
AU  - Marinelli D
AD  - Department of Radiological, Oncological and Pathological Science, Sapienza 
      University of Rome, Rome, Italy.
FAU - Sposetti, Caterina
AU  - Sposetti C
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 
      Milan, Italy.
FAU - Barberi, Vittoria
AU  - Barberi V
AD  - Sapienza Universita di Roma - IRCCS Istituto Nazionale Tumori Regina Elena, 
      RomeItaly.
FAU - Strigari, Lidia
AU  - Strigari L
AD  - Department of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di 
      Bologna, Bologna, Italy.
FAU - Marchetti, Paolo
AU  - Marchetti P
AD  - Department of Oncology and Dermatological Oncology, Istituto Dermopatico 
      dell'Immacolata IDI IRCCS, Rome, Italy.
FAU - Santini, Daniele
AU  - Santini D
AD  - Department of Medico-Surgical Sciences and Biotechnology, Polo Pontino, Sapienza 
      University of Rome, Rome, Italy.
AD  - Medical Oncology A, AOU Policlinico Umberto I, Rome, Italy.
FAU - Fabi, Alessandra
AU  - Fabi A
AD  - Precision Medicine in Senology, Scientific Directorate - Department of Women and 
      Child Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, 
      Italy.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 5384HK7574 (trastuzumab deruxtecan)
RN  - P188ANX8CK (Trastuzumab)
RN  - 0 (Immunoconjugates)
RN  - XT3Z54Z28A (Camptothecin)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Male
MH  - Humans
MH  - Aged
MH  - *Breast Neoplasms/drug therapy
MH  - Retrospective Studies
MH  - Trastuzumab/adverse effects
MH  - *Immunoconjugates
MH  - Camptothecin/*analogs & derivatives
MH  - *Neutropenia
MH  - Nausea
MH  - Receptor, ErbB-2/genetics
PMC - PMC10994255
OTO - NOTNLM
OT  - DE-REAL study
OT  - HER2+
OT  - breast cancer
OT  - trastuzumab deruxtecan
COIS- Andrae Bottticelli has advisory and consulting role for Roche, MSD, Novartis, 
      Pfizer, Lilly, Amgen, BMS, Gliead, Sofos, Daichii, and AstraZeneca. Roberta 
      Capuro reported advisory roles with Roche, Lilly, Novartis, MSD, Gilead, Daiichi 
      Sankyo, and Pierre-Fabre. Simone Scagnoli reported speaker fees from Novartis, 
      Pfizer, Roche, Lilly, BMS, and MSD. Simona Pisegna reported speaker honoraria 
      from Novartis, Lilly, Pfizer, Roche, AstraZeneca, and Gilead. Michelino De 
      Laurentiis reported consulting for Astrazeneca, Amgen, Celgene, Daiichi Sankyo, 
      Eisai, Eli Lilly, Exact-Science, Gilead, MSD, Novartis, Pfizer, Pierre Fabre, 
      Roche, and Seagen. Giuseppe Curigliano reported consultant fee for BMS, Roche, 
      Pfizer, Novartis, Lilly, AstraZeneca, Daichii Sankyo, Merck, Seagen, Ellipsis, 
      and Gilead, and a grant from Merck. Francesco Pantano reported advisory board for 
      Gilead, AstraZeneca, Daiichi Sankyo, and Novartis. Antonella Palazzo reported 
      advisory board/invited speaker for AstraZeneca, Daichii-Sankyo, Novartis, Pfizer, 
      Eli Lilly, and MSD. Claudio Vernieri reported advisory role for Eli Lilly, 
      Novartis, Pfizer, and Daiichi Sankyo; honoraria as a speaker for Eli Lilly, 
      Novartis, Pfizer, Daiichi Sankyo, Istituto Gentili, Accademia di Medicina; and 
      research grants from Roche. Michela Palleschi reported advisory board member for 
      Novartis and Lilly. Giuliana D'Auria reported advisory role for Amgen, Pfizer, 
      Lilly, Novartis, and Eisai. Agnese Fabbri reported advisory and speaker fees from 
      Lilly, Pfizer, Roche, Novartis, and Gilead. Paolo Marchetti has/had a 
      consultant/advisory role for BMS, Roche, Genentech, MSD, Novartis, Amgen, Merck 
      Serono, Pierre-Fabre, and Incyte. Daniele Santini reported advisory board for 
      Angen, Janssen, Astellas, Bayer, Servier, Novartis, MSD. Merck, Pfizer, and 
      Ipsen. Alessandra Fabi reported advisory board for Roche, Pfizer, Novartis, 
      Gilead, Sophos, Seagen, AstraZeneca, Lilly, Pierre Fabre, Exact Science. The 
      other authors indicated no financial relationships.
EDAT- 2023/11/23 18:41
MHDA- 2024/04/08 06:42
PMCR- 2023/11/23
CRDT- 2023/11/23 16:03
PHST- 2023/07/26 00:00 [received]
PHST- 2023/10/09 00:00 [accepted]
PHST- 2024/04/08 06:42 [medline]
PHST- 2023/11/23 18:41 [pubmed]
PHST- 2023/11/23 16:03 [entrez]
PHST- 2023/11/23 00:00 [pmc-release]
AID - 7444338 [pii]
AID - oyad308 [pii]
AID - 10.1093/oncolo/oyad308 [doi]
PST - ppublish
SO  - Oncologist. 2024 Apr 4;29(4):303-310. doi: 10.1093/oncolo/oyad308.