Abstract 55P
Background
Routine methods for MSI/dMMR for CRC pts detection are PCR/IHC, however the data on the benefit of ICI in cases with discordant results is limited. The clinical validity of NGS as a promising approach for MSI detection is currently unclear.
Methods
Patients with MSI+ (PCR) or dMMR (IHC) colorectal cancer (CRC) were eligible (NCT06414304). All patients received immune checkpoint inhibitors (ICI) and had pre-treatment FFPE and liquid biopsy (LB) samples available for central MSI/dMMR testing with PCR/IHC (FFPE) and with NGS (Atlas Pro panel) (FFPE and LB).
Results
A total of 32 patients were included, 22 patients with stages II-III received ICI preoperatively, 10 – for advanced disease; 28 were available for response assessment. ORR in ITT population was 46%. Among 4 patients with discordant results (PCR vs IHC), ORR was 0% (p>0.05). In patients with MSI+ FFPE or MSI+ LB by NGS (n=23), ORR was 57% (p>0.05). Among pts with available LB (n=26), ORR was higher when LB samples were MSI+ (56%) vs MSS (25%) with p>0.05. Among MSI+ by NGS (LB) cases two were pMMR by IHC. Both cases had SD and were MSI+ by PCR and NGS (FFPE). None of the patients had MSI+ by NGS (LB) and MSS by PCR. Patients with DC had a median blood MSI burden of 0.07 (range, 0-0.77), whereas median MSI burden of pts with PD was 3.76 (range, 2.44-5.08) (p=0.03). Table: 55P
ORR by MSI analysis via different methods
| NGS (FFPE) | NGS (FFPE) | NGS (LB) | NGS (LB) | ||
| MSI | MSS | MSI | MSS | ||
| IHC (FFPE) | dMMR | 50% (n=16) | 0% (n=1) | 75% (n=12) | 33% (n=3) |
| IHC (FFPE) | pMMR | 0% (n=3) | n=0 | 0% (n=2) | 0% (n=1) |
| PCR (FFPE) | MSI | 45% (n=20) | 100% (n=1) | 44% (n=16) | 33% (n=3) |
| PCR (FFPE) | MSS | n=0 | 0% (n=1) | n=0 | 0% (n=1) |
Conclusions
Patients with MSI+ by PCR may experience different ICI benefits based on IHC status. Patients with MSI+ LB have better ORR. MSI burden analysis in pre-treatment LB samples is associated with better treatment outcomes. Further research is warranted.
Editorial acknowledgement
Clinical trial identification
NCT06414304.
Legal entity responsible for the study
The authors.
Funding
Russian Science Foundation (Grant №22-75-10154).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
72P - SNCG promotes the malignant progression of hepatocellular carcinoma by activation EGFR signaling and recycling
Presenter: Yue Chen
Session: Cocktail & Poster Display session
Resources:
Abstract
73P - TROP2 amplification is highly present in dedifferentiated liposarcoma: Data from the Cancer Genome Atlas (TCGA) in soft tissue sarcoma
Presenter: Sarah Orlando
Session: Cocktail & Poster Display session
Resources:
Abstract
74P - The influence of genetic phenotype on prognosis of osteosarcoma
Presenter: Nasirov Kamalovich
Session: Cocktail & Poster Display session
Resources:
Abstract
76P - Immune engager compounds screening using CRC patient-derived organoids
Presenter: Claudia Maria A. Pinna
Session: Cocktail & Poster Display session
Resources:
Abstract
77P - Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer
Presenter: Juan Jiménez-Vacas
Session: Cocktail & Poster Display session
Resources:
Abstract
78P - Exploring ecDNA heterogeneity and evolution in non-small cell lung cancer
Presenter: Jeanette Kittel
Session: Cocktail & Poster Display session
Resources:
Abstract
79P - Targeting galectin-9 in BRCA mutant breast cancer
Presenter: Chun Yan So
Session: Cocktail & Poster Display session
Resources:
Abstract
80P - Suppression of glioblastoma progression by FDA-approved central nervous system-accumulating drugs via autophagy modulation and ER stress-induced apoptosis
Presenter: Smita Dey
Session: Cocktail & Poster Display session
Resources:
Abstract
81P - Evaluating the effect of lenvatinib-resistance in hepatocellular carcinoma cells and in lenvatinib-resistant patient-derived PBMCs
Presenter: Luisa Amato
Session: Cocktail & Poster Display session
Resources:
Abstract
82P - Applying computational approaches to build a predictive protein structure and discover novel inhibitors for mitotic serine/threonine kinase BUB1B
Presenter: Joan Glenny Pescov
Session: Cocktail & Poster Display session
Resources:
Abstract