Abstract 193P
Background
Aberrant activation of FGF19-FGFR4 signaling pathway is commonly observed in HCC and correlated with poor prognosis in pts treated with Lenvatinib or Sorafenib at first-line (1L). ICI-based regimens demonstrate superior efficacy and have now become standard of care in 1L treatment of HCC. However, the relationship between FGF19 expression and prognosis in uHCC pts receiving ICI-based initial therapy remains unclear.
Methods
uHCC pts registered from 2019/1/1 to 2023/6/1 at Tongji Hospital were screened, and those who had archived tissue samples and received ICI-based initial therapy with trackable outcome were included. Clinical data were retrospectively collected, and FGF19 status was centrally assessed by IHC. Response and PFS were analyzed based on electronic medical record. Kaplan-Meier curve and log-rank test were employed to compare PFS between two groups.
Results
Totally 608 pts were screened and 102 were eligible for tissue assessment. 68 pts were included in the final analysis, while 34 were excluded due to tissue quality or outcome availability. Out of 68 pts, 94.1% were male, 85.3% had HBV infection, 45.6% BCLC stage C; median age was 49y and median duration of follow-up was 16.8m. Twenty-three were positive for FGF19 (33.8%), and baseline demographics were comparable between FGF19 + and FGF19- groups. mPFS and response rate were 7.9m and 41.7% for all pts, respectively. FGF19+ pts showed significantly shorter mPFS (6.1 vs 11.4 mo; p<0.05; HR=0.45, 0.22-0.89) and a numerically lower response rate (6/18, 33.3% vs 19/42, 45.2%) compared to FGF19 pts. Table: 193P
Comparison of baseline characteristics between FGF19+ and FGF19- groups
| Comparison of baseline characteristics between FGF19+ and FGF19- groups | |||
| Variables, N (%) | FGF19+ (N=23) | FGF19- (N=45) | |
| Age | ≥65 | 2 (8.7) | 2 (4.4) |
| <65 | 21 (91.3) | 43 (95.6) | |
| Sex | Male | 22 (95.6) | 42 (93.3) |
| Female | 1 (4.4) | 3 (6.7) | |
| HBV history | Yes | 21 (91.3) | 44 (97.8) |
| No | 2 (8.7) | 1 (2.2) | |
| Child-Pugh score | A | 21 (91.3) | 43 (93.3) |
| B | 2 (8.7) | 2 (6.7) | |
| BCLC | B | 12 (52.2) | 25 (55.6) |
| C | 11 (47.8) | 20 (44.4) |
Conclusions
This is the first study that revealed the association of FGF19 expression with poor clinical outcome in HCC pts receiving ICI-based treatment, which could serve as an important tool to identify pts at increased risk and inform FGF19/FGFR4 targeted interventions, including combinations, in the treatment of FGF19+ HCC.
Legal entity responsible for the study
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Funding
Chen Xiao-Ping Foundation for The Development of Science and Technology of Hubei Province.
Disclosure
All authors have declared no conflicts of interest.