Phase II Trial of Trifluridine/Tipiracil Plus Irinotecan in Patients with Advanced, Refractory Biliary Tract Carcinoma.

BACKGROUND: We sought to determine the safety and efficacy of trifluridine/tipiracil in combination with irinotecan in a phase II trial setting for refractory, advanced unresectable biliary tract carcinoma (BTC). METHODS: A total of 28 patients (27 were evaluable) with advanced BTCs who progressed on at least one prior systemic therapy were enrolled and were treated with trifluridine/tipiracil 25 mg/m2 (days 1-5 of 14-day cycle) and irinotecan 180 mg/m2 (day 1 of the 14-day cycle). The primary endpoint for the study was 16-week progression-free survival (PFS16) rate. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were pre-specified secondary endpoints. RESULTS: Of 27 patients, PFS16 rate was 37% (10/27; 95% CI: 19%-58%), thereby meeting the criteria for success for the primary endpoint. The median PFS and OS of the entire cohort were 3.9 months (95% CI: 2.5-7.4) and 9.1 months (95% CI: 8.0-14.3), respectively. In the patients evaluable for tumor response (n = 20), the ORR and DCR were 10% and 50%, respectively. Twenty patients (74.1%) had at least one grade 3 or worse adverse event (AE), and 4 patients (14.8%) had grade 4 AEs. A total of 37% (n = 10/27) and 51.9% (n = 14/27) experienced dose reductions in trifluridine/tipiracil and irinotecan, respectively. Delay in therapy was noted in 56% of the patients while 1 patient discontinued the therapy, primarily due to hematologic AEs. CONCLUSION: The combination of trifluridine/tipiracil plus irinotecan is a potential treatment option for patients with advanced, refractory BTCs with good functional status and no targetable mutations. A larger randomized trial is needed to confirm these results. (ClinicalTrials.gov Identifier: NCT04072445).

Postpartum related intrahepatic cholangiocarcinoma with FGFR2 fusion and severe hyperbilirubinemia with response to FGFR inhibitor pemigatinib: case report and review.

Background: Cholangiocarcinoma during postpartum or pregnancy is a rare presentation. There are limited cases reported in the literature. Diagnosis can be delayed as presenting signs and symptoms may be attributed to pregnancy or postpartum state. Case Description: We present the case of a 33-year-old postpartum woman with intrahepatic cholangiocarcinoma with severe hyperbilirubinemia who was found to have fibroblast growth factor receptor 2 (FGFR2)-adenosylhomocysteinase like 1 (AHCYL1) fusion on next-generation sequencing (NGS). She initially was treated with two doses of gemcitabine and cisplatin with increasing hyperbilirubinemia requiring hold of further chemotherapy. NGS showed FGFR2-AHCYL1 fusion, and she was started on the FGFR inhibitor pemigatinib, with dramatically decreasing bilirubin within 10 days. She eventually normalized her bilirubin values and had partial response on follow-up imaging. Conclusions: This is the first report, to our knowledge of response to an FGFR inhibitor in the postpartum setting, as well to show response in the setting of life-threatening hyperbilirubinemia. Our patient did not tolerate standard chemotherapy, likely due to liver dysfunction, but responded to pemigatinib, suggesting that the liver dysfunction was driven by her disease. This case underscores the need to include NGS as part of initial workup to identify important therapeutic targets and increase available lines of therapy, including those patients who are postpartum or pregnant.