A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin in patients with advanced triple negative breast cancer.

DOI
Publisher DOI
PubMed ID
36879012
Abstract
Advanced triple negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience progression 12 months after the initiation of conventional first-line chemotherapy. Approximately two thirds of TNBC express epidermal growth factor receptor 1 (EGFR). We have developed an anti-EGFR targeted nanocontainer drug by inserting anti-EGFR antibody fragments into the membrane of pegylated liposomes (anti-EGFR-ILs-dox). The payload consists of doxorubicin, a standard drug for TNBC. In a first-in-human phase I trial in 26 patients with various advanced solid malignancies, anti-EGFR-ILs-dox has shown little toxicity and encouraging efficacy. In this single-arm phase II trial, we assessed the efficacy of anti-EGFR-ILs-dox as first-line therapy in patients with advanced, EGFR + TNBC. The primary endpoint was progression-free survival at 12 months (PFS12m). Secondary endpoints included overall response rate (ORR), duration of response (DOR), time to progression (TTP), overall survival (OS) and adverse events (AEs). 48 patients received anti-EGFR-ILs-dox 50 mg/m2 iv, on day one of a 28 days-cycle until progression. The Kaplan-Meier estimate for PFS12m was 13% (one-sided 90% CI 7%, 95% CI [5%, 25%]), median PFS was 3.5 months (95% CI 1.9, 5.4). The trial has not reached its primary endpoint. There were no new toxicity signals. Based on these results, anti-EGFR-ILs-dox should not be further developed for TNBC. It remains an open question whether anti-EGFR-ILs-dox would offer more opportunities in other EGFR-expressing malignancies, where targeting this receptor has already shown anticancer effects.Trial registration: This trial was registered at clinicaltrials.gov: NCT02833766. Registered 14/07/2016.
Date Issued
2023-03-06
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
Mamot, Christoph
Wicki, Andreas
Hasler-Strub, Ursula
Riniker, Salome
Li, Qiyu
Holer, Lisa
Bärtschi, Daniela
Zaman, Khalil
von Moos, Roger
Dedes, Konstantin J
Boos, Laura A
Bodmer, Alexandre
Ritschard, Reto
Obermann, Ellen C
Tzankov, Alexandar
Ackermann, Christoph
Membrez-Antonioli, Véronique
Zürrer-Härdi, Ursina
Caspar, Clemens B
Deuster, Stefanie
Senn, Martin
Winterhalder, Ralph
Rochlitz, Christoph
Additional Credits
Journal
Scientific Reports
Publisher
Nature Publishing Group
ISSN
2045-2322
Access(Rights)
open.access
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