E181: Incidence and Prognostic Value of Actionable Alterations in Early-Stage Resectable Cholangiocarcinoma

Targeted therapy for actionable alterations in advanced cholangiocarcinoma (CCA) has revolutionized 2^nd and 3^rd line treatment algorithms. Their application in early-stage CCA is not defined. The incidence and prognostic value of actionable alterations in patients (pts) with early-stage, resected CCA is unknown.

Methods:

The Cholangiocarcinoma Foundation and Ciitizen® (a wholly owned subsidiary of Invitae Corporation) collaboratively launched a registry platform that directly consents pts and collects comprehensive medical records. De-identified data including clinical characteristics, molecular testing, interventions, and outcomes have been extracted and standardized for research use on 400 pts. We identified pts who underwent resection of non-metastatic CCA and underwent biomarker testing. Actionable alterations recorded included FGFR2 fusion/rearrangement, IDH1 mutation, HER2 amplification, BRAF mutation, MSI-high, and TMB-high. Primary outcome was recurrence-free survival (RFS).

Results:

Of 400 pts, 137 underwent resection for CCA. When comparing pts with advanced disease to those who underwent resection, there was a similar frequency of biomarker testing: 94.3% (n=248) vs 83.9% (n=115) and presence of actionable alterations: 38.7% (n=96) vs. 33.0% (n=38). When considering pts with non-metastatic, resected disease who underwent biomarker testing (n=104), the mean age was 59.2 yrs, 66 (63.5%) were females, and 60 (57.7%) had intrahepatic CCA (iCCA), 42 (40.4%) had extrahepatic CCA, and 2 (1.9%) were not otherwise specified. A majority received biomarker testing before or at surgery (n=89, 85.6%). 34 pts (32.7%) had actionable alterations: FGFR2: n=7 (6.7%), IDH1: n=16 (15.4%), HER2: n=5 (4.8%), BRAF: n=0, MSI-high: n=3 (2.9%), TMB-high: n=8 (7.7%). FGFR2 fusion/rearrangement and IDH1 mutations were only identified in iCCA. Pts with a FGFR2 fusion/rearrangement were younger (49.9 vs 59.8 yrs; p=0.028) and all were female. Although not statistically significant, the presence of an FGFR2 fusion/rearrangement was associated with a trend towards improved median RFS (32.0 vs 17.3 mos; p=0.19; Fig 1) for pts with iCAA.

Conclusions:

Of pts with early-stage, resected CCA, a majority underwent molecular profiling before or at surgery. As expected, FGFR2 fusion/rearrangement and IDH1 mutations were only present in iCCA. A FGFR2 fusion/rearrangement was seen in young, female pts and was associated with a trend towards longer RFS. Clinical trials are needed to assess the value of administering neoadjuvant or adjuvant targeted therapy to this patient population.