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
132P - Deciphering aggressive behavior in uterine inflammatory myofibroblastic tumors: Clinicopathological and molecular analysis
Presenter: Nikola Hajkova
Session: Cocktail & Poster Display session
Resources:
Abstract
133P - Exploring genomic instability at the single-cell level using a new method for the inference of copy number alterations
Presenter: Lucrezia Patruno
Session: Cocktail & Poster Display session
Resources:
Abstract
134P - SPICE: Probabilistic reconstruction of copy-number evolution in cancer
Presenter: Abigail Bunkum
Session: Cocktail & Poster Display session
Resources:
Abstract
135P - Revealing the third kind of pathway of colorectal cancer developing from laterally spreading tumors
Presenter: Jianshe Yang
Session: Cocktail & Poster Display session
Resources:
Abstract
136P - Investigating the evolutionary and regulatory dynamics of acquired resistance to BTK inhibitors in activated B-cell diffuse large B-cell lymphoma cells
Presenter: Luminita Ruje
Session: Cocktail & Poster Display session
Resources:
Abstract
137P - PHANTOM: Bootstrap inference of single-cell tumour phylogenies by integrating sequencing read counts
Presenter: Rija Zaidi
Session: Cocktail & Poster Display session
Resources:
Abstract
138P - Analysis of master regulatory transcription factors and their associated transcriptomic profiles in SCLC patients
Presenter: Janik Riese
Session: Cocktail & Poster Display session
Resources:
Abstract
139P - Rewiring of cis-regulatory and kinase signalling networks in acalabrutinib-resistant ABC DLBCL cells
Presenter: Pavel Artemov
Session: Cocktail & Poster Display session
Resources:
Abstract
140P - MYC subgroups delineate specific transcriptomic landscape and shape response to radiotherapy in SCLC
Presenter: Caterina de Rosa
Session: Cocktail & Poster Display session
Resources:
Abstract
141P - An unconditionally dynamic culture system for cancer stem cell
Presenter: Ya-Juan Zhu
Session: Cocktail & Poster Display session
Resources:
Abstract