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.
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