Abstract 67P
Background
Intrahepatic cholangiocarcinoma (iCCA) is a subset of cholangiocarcinoma. Poor prognosis and limited treatment options are the major clinical challenges for iCCA patients. Fibroblast growth factor receptor 2 (FGFR2) has emerged as a tumorigenic driver gene in iCCA and pemigatinib had approved for the target treatment of FGFR2 fusion/rearrangement.
Methods
Deep sequencing targeting 450 cancer genes was performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) for genomic alteration identification. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Statistical analysis was performed by Fisher’s exact test.
Results
A total of 92 Chinese resectable iCCA patients, including 35 females and 57 males, were enrolled in this study. The most commonly altered genes included TP53 (36%, 33/92), KRAS (27%, 25/92), ARID1A (18%, 17/92), CDKN2A (15%, 14/92), TERT (14%, 13/92), PBRM1 and BAP1 (13%, 12/92, for both), FGFR2 (12%, 11/92) and BRAF (11%, 11/92). Nine (9.8%) iCCA patients harbored FGFR2 fusion. Consistent with previous reports, patients with FGFR2 fusion tend to occur more commonly in females (17% vs 5%, P=0.08). The average TMB value of patients with FGFR2 fusion was 2.0 muts/Mb (ranged 0.6-4.3 muts/Mb), and 6 muts/Mb (ranged 0-45.2 muts/Mb) in patients without FGFR2 fusion. There was no difference in TMB between patients with or without FGFR2 fusion (P=0.35). In FGFR2 fusion patients, the most frequent mutated genes were BAP1 (33%, 3/9) and PIK3CA (33%, 3/9). Interestingly, Co-mutation analysis showed that FGFR2 fusion were significantly associated with the mutation of PIK3CA (P < 0.01), but mutually exclusive with the mutation of KRAS (P < 0.015) in iCCA. There was no significant difference in disease free survival (DFS) between patients with FGFR2 fusion or not (P=0.86).
Conclusions
The identification of FGFR2 fusion indicated that 9.8% Chinese iCCA patients had the opportunity to benefit from FGFR2 fusion targeting drugs. DFS analysis of FGFR2 fusion patients shows that the molecular mechanism of Chinese patients with iCCA is different from that of western countries. However, further study with expansion cohort is still needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Shandong Provincial Hospital Affiliated to Shandong First Medical University.
Funding
Science and Technology Development Project of Jinan City (201907073).
Disclosure
All authors have declared no conflicts of interest.