Abstract 268P
Background
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 a progression 12 months after the initiation of conventional first-line chemotherapy. Approximately 2/3 of TNBC express epidermal growth factor receptor 1 (EGFR) on malignant cells. 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 breast cancer, including TNBC. In a first-in-human trial of 26 patients diagnosed with various advanced solid malignancies, anti-EGFR-ILs-dox has shown little toxicity and encouraging signs of efficacy. In the current single-arm phase II trial, the main objective was to determine the efficacy of anti-EGFR-ILs-dox as first-line therapy in patients with advanced EGFR+ TNBC.
Methods
48 patients were treated with anti-EGFR-ILs-dox 50 mg/m2 i.v., on day one of a 28 days cycle until progression. The primary endpoint was progression-free survival at 12 months (PFS12m). For the statistical analysis, we tested the null hypothesis PFS12m ≤25% against the alternative hypothesis PFS12m ≥40%. The reference for the PFS12m of 25% for the null hypothesis was the TNBC subgroup of the ATHENA trial. Secondary endpoints included ORR, DOR, TTP, PFS, OS and AE.
Results
In this multicenter trial, the Kaplan-Meier estimate for PFS12m was 13% (95% CI: 5-25%). The median PFS was 3.5 months (95% CI: 1.9, 5.4). Thus, the trial has not reached its primary endpoint. The observed PFS12m is comparable to the one observed in a trial with Nab-paclitaxel in TNBC (17.7%). There were no new toxicity signals compared to the phase 1 trial.
Conclusions
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 EGFR has already shown anticancer effects.
Clinical trial identification
NCT02833766.
Editorial acknowledgement
Legal entity responsible for the study
Swiss Group for Clinical Cancer Research.
Funding
Merrimack.
Disclosure
R. von Moos: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Polyphor; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Vifor. All other authors have declared no conflicts of interest.