23P Prediction of response to atezolizumab plus nab-paclitaxel in unresectable locally advanced triple-negative breast cancer (TNBC): The clinical usefulness of PD-L1 mRNA expression in plasma-derived exosomes

Abstract

Background: The number of early clinical trials evaluating immunotherapies (IT) has increased exponentially over the last decade. These agents expose to adverse events (AE), which have been largely described with immune checkpoint blockers (ICB) as a monotherapy. However, the safety profile of IT other than ICB or in combination, have been poorly characterized. Here, we comprehensively analyze the safety profile of IT in phase I/II (P1/2) trials when used as a monotherapy (M) or in combination (C) with other anti-cancer agents, and compare it to the one of other anticancer agents assessed in the same patient (pt) population. Methods: All consecutive pts treated in a P1/2 trial at the Gustave Roussy Drug Development Department between Jan 2008 and Aug 2020 were included. Pt and trial characteristics, AEs of any grade (G) and any type occurring at any cycle on trial, dose administered and treatment modifications were described in the following subgroups: IT as a M (IT-M), targeted therapy (TT) as a M (TT-M), IT in C (IT-C), TT in C (TT-C), other.

Molecular Characterization of Exosomes for Subtype-Based Diagnosis of Breast Cancer

“…Similar to the analysis of the samples of ER + BC patients, peak currents obtained in the samples of the HDs were much lower than those in the samples of TNBC patients (Figure 5E), in agreement with the relative PD-L1 mRNA levels as determined by qRT−PCR (Figure S43). 47,48 The mean value of the peak currents of the TNBC patients (0.429 μA) was significantly higher than that of the HDs (0.126 μA) and was increased as the disease progressed (0.223 μA for stages I and II vs 0.553 μA for stages III and IV) (Figure 5F). The peak currents obtained with clinical samples of TNBC patients in an advanced stage were higher than those obtained with the ER + subtype, as determined using MDA-MB-231 cell-derived membrane vesicles (Figure S44).…”