In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4101-4101
Abstract:
4101 Background: Microsatellite instability-high (MSI-H) status is a unique genomic state with encouraging effects of PD-1-based therapy in patients with advanced cancer. Cholangiocarcinoma is often driven by genetic mutations. However, the genomic characterization and translational medicine of MSI-H are not clear. Methods: In this study, 881 Chinese patients with cholangiocarcinoma (582 intrahepatic cholangiocarcinoma and 299 extrahepatic cholangiocarcinoma) were enrolled and their genomes were investigated using panel sequencing or whole-exome sequencing. Clinicopathological and genomic features as well as PD-1 inhibitor-based immunotherapy were analyzed by MSI status in patients with cholangiocarcinoma. Results: Overall, 47 (5.3%) cholangiocarcinoma patients were identified as MSI-H patients after enrichment enrollment. Intrahepatic cholangiocarcinoma (ICC) accounted for 74.47% (35/47) of MSI-H patients. Clinicopathological parameters showed younger, ICC-dominated, and more positive PD-L1 expression in MSI-H patients. In the genome of MSI-H cholangiocarcinoma, ACVR2A (75.00%), ARID1A (75.0%), KMT2D (72.2%), TGFBR2 (63.9%), PBRM1 (58.3%), RNF43 (55.6%), TP53 (52.8%) ), ARID1B (47.2%) had a higher mutation frequency. Comparing the SNV and INDEL mutation in the genome, the differential genes between MSI-H and MSS were ARID1A, ACVR2A, KMT2D, TGFBR2, PBRM1, RNF43, LRP1B, ARID1B, etc., respectively. In addition, the differential mutation pathways of MSI-H showed that the mutation rate of DDR, SWI/SNF CellCycle, HRD and other pathways was significantly higher than that of MSS samples. The tumor mutation burden (TMB) in MSI-H patients was significantly higher than that in MSS (P 〈 0.001). In a cohort of 151 CCA patients who received PD-1 inhibitor-based immunotherapy, 19 patients with MSI-H cholangiocarcinoma were found to have a favorable prognosis (1-year survival rate 68.4%). Compared with 132 MSS cholangiocarcinoma patients, Patients with MSI-H cholangiocarcinoma had significantly prolonged OS (Not reach vs. 13.4m, P 〈 0.001, HR=0.17, P 〈 0.001) and high clinical benefit (CBR) (OR=8.16, P 〈 0.001). In this immunotherapy cohort, ≥2 DDR pathway genes and ≥2 SWI/SNF pathway genes mutations, positive PD-L1 expression and TMB-H were also associated with better OS and CBR (both P 〈 0.05). Conclusions: MSI-H cholangiocarcinoma has distinct genomic features, and the effect of PD-1 inhibitors immunotherapy is excellent to these patients. Clinical trial information: NCT03892577.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.4101
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2022
detail.hit.zdb_id:
2005181-5
Permalink
