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
142P - Lipidomic signature in response to omega-3 fatty acids and γ-linolenic acid supplementation in breast cancer patients receiving aromatase inhibitors
Presenter: Vesna Vucic
Session: Cocktail & Poster Display session
Resources:
Abstract
143P - A tailored histology-driven molecular profiling algorithm proposal for salivary gland cancers
Presenter: Simone Rota
Session: Cocktail & Poster Display session
Resources:
Abstract
144P - Is it time to incorporate next generation sequencing of body fluids for detection of circulating tumor DNA (ctDNA) alterations?
Presenter: Aditya Shreenivas
Session: Cocktail & Poster Display session
Resources:
Abstract
145P - Unveiling the molecular landscape of head and neck cancer: Pathway dysregulations and potential therapeutic targets
Presenter: Rajeev Vijayakumar
Session: Cocktail & Poster Display session
Resources:
Abstract
146P - ESR1 fusions as potential mechanism of resistance to endocrine therapy in metastatic breast cancer
Presenter: Sewanti Limaye
Session: Cocktail & Poster Display session
Resources:
Abstract
147P - Clinical characteristics and outcomes in non-small cell lung cancer patients harboring rare mutations: A single center real-world data
Presenter: Ana Rita Freitas
Session: Cocktail & Poster Display session
Resources:
Abstract
148P - Diversity of genomic mechanisms of resistance to endocrine therapy in ER+ breast cancer
Presenter: Prithika Sritharan
Session: Cocktail & Poster Display session
Resources:
Abstract
149P - Assessing treatment options for gynaecological cancers (GC) using next-generation sequencing (NGS): A real-world analysis
Presenter: Álvaro García
Session: Cocktail & Poster Display session
Resources:
Abstract
150P - Prevalence of DPYD variants in 1478 cancer patients receiving fluoropyrimidine chemotherapy: A real-world data analysis
Presenter: Bahaaeldin Baraka
Session: Cocktail & Poster Display session
Resources:
Abstract
151P - Unravelling the limitations of next-generation sequencing (NGS)-based liquid biopsy (LB) across solid tumors: The PREICO-LB project
Presenter: Cinta Hierro
Session: Cocktail & Poster Display session
Resources:
Abstract