Introduction
EGFR-expressing solid, hyperpermeability, cancer, Breast cancer, cancer death, toxicity, TNBC, TNBC tumor, Toxicity, tumors, Kaposi's sarcomaIn
CPS, CANCER, BREAST CANCER, BREAST CANCER
Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, accounting for 25% of all new cancer cases and 15.5% of cancer deathsImmunotherapy (in combination with chemotherapy) is available for those with advanced TNBC that express PD-L1 and has shown a significant overall survival benefit in patients with CPS ≥ 10%Liposomal encapsulation of drugs, in particular doxorubicin, is used to alter the tissue distribution and pharmacokinetics of the drug, increasing its therapeutic index by making use of the hyperpermeability of vascular structures in the proximity of neoplastic tissue. In clinical settings, pegylated liposomal doxorubicin has shown efficacy, first in the treatment of Kaposi's sarcomaIn order to achieve better efficacy and reduce toxicity, more specific delivery of liposomal doxorubicin to the target cells would be desirable. Up to 70% of TNBC express the epidermal growth factor receptor (EGFR), a tyrosine kinase receptor of the ErbB family, which is abnormally activated in many epithelial tumorsWhile blocking the EGF receptor by a mAb does not lead to clinical benefit so far, we hypothesized that EGFR remains a valid target for drug delivery systems in breast cancer, due to the high frequency and expression levels of EGFR on the surface of TNBC tumor cells. Therefore, we constructed anti-EGFR targeted immunoliposomes by covalently inserting cetuximab fragments into the lipid layer of pegylated liposomal doxorubicin, creating a stable and robust drug carrier with a ligand, a mAb fragment, directing the encapsulated doxorubicin towards the target. In a series of preclinical experiments, we have shown that anti-EGFR targeted immunoliposomes may enhance drug efficacy in vivoBased on these findings, we performed a classic dose finding phase I trial with this nanocontainer in patients with EGFR-expressing solid tumors. Toxicity was low and there were signs of clinical activity in heavily pretreated patientsThe main objective of this trial, SAKK 24/14, is to determine the efficacy of anti-EGFR-ILs-dox as a first-line therapy option in this patient population.