720P - Second line therapy with sunitinib as single agent in patients with advanced intrahepatic cholangiocarcinoma (update on SUN-CK phase II trial)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Hepatobiliary Cancers
Presenter Cindy Neuzillet
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors C. Neuzillet1, J. Seitz2, L. Fartoux3, D. Malka4, G. Lledo5, A. Tijeras-Raballand6, A. De Gramont6, M. Ronot7, M. Bouattour1, C. Dreyer1, A. Amin8, P. Bourget8, A. Hadengue9, N. Roldan9, B. Chibaudel9, E. Raymond1, S. Faivre1
  • 1Medical Oncology, Hôpital Beaujon, 92110 - Clichy/FR
  • 2Oncologie Digestive, Hôpital de La Timone, Marseille/FR
  • 3Hepatology, Hôpital Saint-Antoine, 75000 - PARIS/FR
  • 4Oncology, Institut Gustave Roussy, Villejuif/FR
  • 5Gastroenterology, Hôpital privé Jean Mermoz, LYON/FR
  • 6Translational Department, AAREC Filia Research, Boulogne-Billancourt/FR
  • 7Radiological Unit, Hôpital Beaujon, 92110 - Clichy/FR
  • 8Department Of Clinical Pharmacy, GH Necker-Enfants Malades, 75743 - PARIS/FR
  • 9Medical Oncology, GERCOR-IRC, Paris/FR

Abstract

Aim

Beyond platinum-based first line chemotherapy for advanced cholangiocarcinoma (CK), second line 5FU-based treatments yield median progression-free survival (PFS) of <3 months and median overall survival (OS) of 6 months, warranting innovative treatment options. Intrahepatic CK subtypes overexpress VEGF, providing a rationale for investigating sunitinib in patients (pts) who failed platinum-based therapy.

Methods

This multicenter phase 2 study enrolled pts with locally advanced intrahepatic CK failing prior first-line platinum-based chemotherapy, ECOG PS 0-1, and adequate liver function with bilirubin <1.5ULN. Sunitinib was given at the continuous daily dose of 37.5 mg. OS was expected >6.3 months (primary objective) other endpoints being PFS, response (RECIST 1.1 & Choi criteria), safety, pharmacokinetics (PK), and pharmacodynamic (PD) biomarkers (VEGFA, VEGFC, sKIT, HGF, SDF1, and osteopontin).

Results

Among 51 pts yet enrolled in this ongoing trial, 34 are currently evaluable for safety and efficacy. Median age was 62 years (range 36–80), 19 females/15 males were included, and ECOG PS was 0/1 in 23/11 pts. With a median follow-up of 15.4 months and a median duration of treatment of 3.8 months, the median OS was 9.6 months [95%CI: 5.8-13.1], exceeding the primary objective. Five pts (15%) had partial responses and 24 stable diseases (71%) by RECIST (disease control rate 85%) with 10 pts having disease control > 6 months (range 6-14 months). Among 12 evaluable patients for Choi criteria, 11 (92%) had objective responses. Median PFS was 5.2 months. Frequently reported 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 24% of patients (neutropenia 8 pts, thrombocytopenia 7 pt), Gr 3 hypertension was observed in 7 pts, and Gr 3 asthenia in 4 pts. PK & PD data will be updated at the meeting.

Conclusions

Sunitinib (continuous daily dose of 37.5 mg) is well tolerated and shows promising activity with 9.6 months OS in second line therapy in pts with intrahepatic advanced CK.

Disclosure

J. Seitz: Honoraria Support from: Merck Serono, Novartis, Amgen, Sanofi-Aventis, Pfizer, Amgen SAS, Bayer-Schering-Pharma, Lilly; L. Fartoux: Honoraria Support from: Bayer and Bristol Myer Squibb; D. Malka: Grant Support from: Amgen, Roche, Merck Serono, Sanofi-Aventis Honoraria Support from: Merck Serono, Ipsen, Celgene, Novartis, Amgen, Roche, Sanofi-Aventis, Imclone, Teva, Keocyt, Boehringer-Ingelheim; M. Bouattour: Honoraria Support from: Bayer; E. Raymond: Honoraria Support from: Bayer, Pfizer, Novartis; S. Faivre: Honoraria Support from: Bayer, Pfizer, Novartis; All other authors have declared no conflicts of interest.