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Multicenter Study
. 2024 Apr 4;29(4):303-310.
doi: 10.1093/oncolo/oyad308.

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

Andrea Botticelli  1 , Roberta Caputo  2 , Simone Scagnoli  1 , Simona Pisegna  3 , Michelino De Laurentiis  2 , Giuseppe Curigliano  4   5 , Matteo Lambertini  6   7 , Francesco Pantano  8 , Antonella Palazzo  9 , Ida Paris  10 , Claudio Vernieri  11   12 , Beatrice Tedesco  13 , Marianna Giampaglia  13 , Michela Palleschi  14 , Zelmira Ballatore  15 , Daniele Alesini  16 , Giuliana D'Auria  17 , Agnese Fabbri  18 , Luigi Rossi  19 , Annarita Verrazzo  2 , Roberta Scafetta  8 , Daniele Marinelli  1 , Caterina Sposetti  11 , Vittoria Barberi  20 , Lidia Strigari  21 , Paolo Marchetti  22 , Daniele Santini  23   24 , Alessandra Fabi  25
Affiliations
Multicenter Study

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

Andrea Botticelli et al. Oncologist. .

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.

Keywords: DE-REAL study; HER2+; breast cancer; trastuzumab deruxtecan.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Best response in the overall population. Response distribution according to RECIST 1.1 criteria.
Figure 2.
Figure 2.
PFS in the whole study population. Kaplan-Meier estimates of PFS in the overall population. mPFS was 16 months. The gray area represents the confidence interval. Tick marks represent data censored at the last time the patient was known to be alive.
Figure 3.
Figure 3.
PFS according to T-DXd treatment line. Kaplan-Meier estimates of PFS in the I/II line versus subsequent lines. mPFS was 17 versus 15 months (P = .098). The colored area represents the confidence interval. Tick marks represent data censored at the last time the patient was known to be alive.
Figure 4.
Figure 4.
PFS according to HR status. Kaplan-Meier estimates of PFS in HR- versus HR+. mPFS was 17 versus 15 months (P = .75). The colored area represents the confidence interval. Tick marks represent data censored at the last time the patient was known to be alive.
Figure 5.
Figure 5.
OS in overall population. Kaplan-Meier estimates of OS in the overall population. mOS was 20 months. The gray area represents the confidence interval. Tick marks represent data censored at the last time the patient was known to be alive.
See this image and copyright information in PMC

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