PMID- 36879012
OWN - NLM
STAT- MEDLINE
DCOM- 20230308
LR  - 20230420
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Mar 6
TI  - A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin 
      in patients with advanced triple negative breast cancer.
PG  - 3705
LID - 10.1038/s41598-023-30950-z [doi]
LID - 3705
AB  - 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/m(2) 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.
CI  - (c) 2023. The Author(s).
FAU - Mamot, Christoph
AU  - Mamot C
AD  - Cantonal Hospital Aarau, Tellstrasse 25, 5001, Aarau, Switzerland. 
      christoph.mamot@ksa.ch.
FAU - Wicki, Andreas
AU  - Wicki A
AD  - University and University Hospital Zurich, Ramistrasse 100, 8091, Zurich, 
      Switzerland. andreas.wicki@usz.ch.
FAU - Hasler-Strub, Ursula
AU  - Hasler-Strub U
AD  - Cantonal Hospital Graubunden, Chur, Switzerland.
FAU - Riniker, Salome
AU  - Riniker S
AD  - Tumor and Breast Center East, St. Gallen, Switzerland.
FAU - Li, Qiyu
AU  - Li Q
AD  - Competence Center of the Swiss Group for Clinical Cancer Research (SAKK), Bern, 
      Switzerland.
FAU - Holer, Lisa
AU  - Holer L
AD  - Competence Center of the Swiss Group for Clinical Cancer Research (SAKK), Bern, 
      Switzerland.
FAU - Bartschi, Daniela
AU  - Bartschi D
AD  - Competence Center of the Swiss Group for Clinical Cancer Research (SAKK), Bern, 
      Switzerland.
FAU - Zaman, Khalil
AU  - Zaman K
AD  - University Hospital Lausanne, Lausanne, Switzerland.
FAU - von Moos, Roger
AU  - von Moos R
AD  - Cantonal Hospital Graubunden, Chur, Switzerland.
FAU - Dedes, Konstantin J
AU  - Dedes KJ
AD  - Breast Center Zurichsee, Zurich, Switzerland.
FAU - Boos, Laura A
AU  - Boos LA
AD  - University and University Hospital Zurich, Ramistrasse 100, 8091, Zurich, 
      Switzerland.
FAU - Novak, Urban
AU  - Novak U
AD  - Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
FAU - Bodmer, Alexandre
AU  - Bodmer A
AD  - University Hospital Geneva, Geneva, Switzerland.
FAU - Ritschard, Reto
AU  - Ritschard R
AD  - University Hospital Basel, Basel, Switzerland.
FAU - Obermann, Ellen C
AU  - Obermann EC
AD  - University Hospital Basel, Basel, Switzerland.
FAU - Tzankov, Alexandar
AU  - Tzankov A
AD  - University Hospital Basel, Basel, Switzerland.
FAU - Ackermann, Christoph
AU  - Ackermann C
AD  - Spital STS AG, Thun, Switzerland.
FAU - Membrez-Antonioli, Veronique
AU  - Membrez-Antonioli V
AD  - Hopital du Valais, Hopital de Sion, Sion, Switzerland.
FAU - Zurrer-Hardi, Ursina
AU  - Zurrer-Hardi U
AD  - Cantonal Hospital Winterthur, Winterthur, Switzerland.
FAU - Caspar, Clemens B
AU  - Caspar CB
AD  - Cantonal Hospital Baden, Baden, Switzerland.
FAU - Deuster, Stefanie
AU  - Deuster S
AD  - University Hospital Basel, Basel, Switzerland.
FAU - Senn, Martin
AU  - Senn M
AD  - University Hospital Basel, Basel, Switzerland.
FAU - Winterhalder, Ralph
AU  - Winterhalder R
AD  - Hospital Lucerne, Lucerne, Switzerland.
FAU - Rochlitz, Christoph
AU  - Rochlitz C
AD  - University Hospital Basel, Basel, Switzerland.
LA  - eng
SI  - ClinicalTrials.gov/NCT02833766
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20230306
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Liposomes)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Humans
MH  - *Liposomes
MH  - *Triple Negative Breast Neoplasms/drug therapy
MH  - Drug Delivery Systems
MH  - ErbB Receptors
MH  - Doxorubicin/adverse effects
PMC - PMC9988854
COIS- K. Dedes: advisory honoraria: AstraZeneca, Daiichi, Novartis. The other authors 
      declare that they have no competing interests.
EDAT- 2023/03/07 06:00
MHDA- 2023/03/09 06:00
PMCR- 2023/03/06
CRDT- 2023/03/06 23:19
PHST- 2022/10/04 00:00 [received]
PHST- 2023/03/03 00:00 [accepted]
PHST- 2023/03/06 23:19 [entrez]
PHST- 2023/03/07 06:00 [pubmed]
PHST- 2023/03/09 06:00 [medline]
PHST- 2023/03/06 00:00 [pmc-release]
AID - 10.1038/s41598-023-30950-z [pii]
AID - 30950 [pii]
AID - 10.1038/s41598-023-30950-z [doi]
PST - epublish
SO  - Sci Rep. 2023 Mar 6;13(1):3705. doi: 10.1038/s41598-023-30950-z.