Sunitinib as second-line treatment in patients with advanced intrahepatic cholangiocarcinoma (SUN-CK phase II trial): Safety, efficacy, and updated translational results

• Published in: Journal of clinical oncology Vol. 33; no. 3_suppl; p. 343
• Main Authors: Neuzillet, Cindy, Seitz, Jean-François, Fartoux, Laetitia, Malka, David, Lledo, Gérard, Tijeras-Raballand, Annemilai, De Gramont, Armand, Ronot, Maxime, Bouattour, Mohamed, Dreyer, Chantal, Amin, Alexandre, Brunisholz - Bourget, Philippe, Hadengue, Alexandra, Roldan, Nelly, Chibaudel, Benoist, Raymond, Eric, Faivre, Sandrine J.
• Format: Journal Article
• Language: English
• Published: 20.01.2015
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2015.33.3_suppl.343

Abstract only 343 Background: There is no validated option beyond gemcitabine plus platinum standard first-line combination for advanced cholangiocarcinoma (CK). Second-line 5FU-based chemotherapy yields a median progression-free survival (PFS) and overall survival (OS) of 3 and 6-7 months, respectively. Intrahepatic CK subtypes overexpress VEGF, providing a rationale for testing sunitinib as second-line treatment in patients (pts) with advanced intrahepatic CK. Methods: A multicenter phase 2 study was designed for pts with locally advanced or metastatic intrahepatic CK after failure of first-line gemcitabine-based chemotherapy. Sunitinib was given at the dose of 37.5 mg/day continuously until disease progression or limiting toxicity. Pts were required to be ECOG PS 0-1 and with adequate liver function (alkaline phosphatase and transaminases < 5ULN, bilirubin <1.5ULN). Main objective was to exceed a median OS of 6.3 months. Secondary endpoints were PFS, response (RECIST 1.1 & Choi criteria), safety, pharmacokinetics (PK) and biomarker analysis (VEGFA, VEGFC, sKIT, HGF, SDF1, and osteopontin). Results: 53 pts were enrolled, with 34 pts evaluable for intermediate safety and efficacy analysis. Median age was 62 years (range 36–80), with 19 females/15 males. ECOG PS was 0/1 in 23/11 pts. Sixteen pts had prior surgical resection and 8 pts received adjuvant chemotherapy. Five pts (15%) had partial responses and 24 stable diseases (71%) by RECIST (disease control rate 85%). Ten pts had disease control > 6 months (range 6-14 months). With a median follow-up of 15.4 months, median OS was 9.6 months [95%CI: 5.8-13.1]. Median PFS was 5.2 months. Frequent adverse events were grade (Gr) 1-2 asthenia (80% of pts), mucositis (80%), diarrhea (60%), and hand-foot syndrome (43%). Gr 3/4 asymptomatic hematological toxicity occurred in 25% of pts (neutropenia n=8, thrombocytopenia n=7), Gr 3 hypertension was observed in 7 pts, and Gr 3 asthenia in 4 pts. Updated PK and biomarker analysis will be presented at the meeting. Conclusions: Second line sunitinib is well tolerated and shows promising activity with a 9.6-month OS in pts with advanced intrahepatic CK. Clinical trial information: NCT01718327.