143P - Genomic characterization and outcomes of patients with primary sclerosing cholangitis-related cholangiocarcinoma

Background

Cholangiocarcinoma (CCA) is the leading cause of death in patients (pts) with primary sclerosing cholangitis (PSC). PSC-related CCA is rare, and there has been no clinical analysis of survival outcomes following surgery, radiation therapy (RT), or systemic therapy. Risk of autoimmune disease flare with immunotherapy also has yet to be reported. We aim to characterize treatment responses and clinical outcomes in relation to tumor mutational profiles.

Methods

We conducted a retrospective analysis of clinical outcomes data and next-generation sequencing (NGS) data at MD Anderson Cancer Center in pts with PSC-related CCA. Patient characteristics were compared using Fisher’s exact test and Mann-Whitney U. Progression-free survival (PFS), recurrence-free survival (RFS), and overall survival (OS) were assessed using the log-rank test.

Results

30 patients available NGS data. The most frequent mutations were both KRAS and TP53 at 13 (43%) followed by CDKN2A at 4 (13%) then both SMAD4 and ARID1A at 3 (10%); 8 pts had KRAS and TP53 mutations. Those treated with localized therapy had statistically significant difference in OS compared to systemic therapy only (Table 143P). Patients who received RT, ablation, or Y90 had no G3/4 hepatic toxicity. No statistically significant differences were observed in PFS for systemic therapies (Table 143P). Median OS of those with KRAS or TP53 mutation was 13.8 months while that of those without KRAS or TP53 was 22.7 months (p=0.0034). Pts with TP53 or KRAS mutations trended toward worse PFS on 1^st line systemic therapy but had no statistical difference. Nine (9) pts received immunotherapy. Four had concurrent autoimmune enteropathy; autoimmune disease flare did not occur. Table: 143P

Treatment outcomes

Conclusions

KRAS and TP53 mutations are the most common mutations and a poor prognostic marker in PSC-related CCA. No flare of autoimmune diseases occurred on immunotherapy. Selected patients who underwent local therapy outperformed those who did not.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

MD Anderson Cancer Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.