Patients with non-resectable intra-hepatic cholangiocarcinoma (ICC) have a bad prognosis, and the efficacy of chemotherapy is limited. SIRT is a promising treatment option in hepatic tumors. In ICC there is no prospective studies of combination SIRT with chemotherapy.
This phase II single-arm study prospectively included patients with non-resectable ICC (liver-only or limited extra-hepatic disease) in 7 centers. Patients received Cisplatin 25mg/m2 and Gemcitabine 1000mg/m2 (reduced to 300mg/m2 the cycles just before and following SIRT) day 1 and 8 of a 21-days cycles. SIRT was delivered during cycle 1 (unilobar disease), or cycles 1 and 3 (bilobar disease). Primary objective was response rate (RR) at 3 months according to RECIST 1.1, with the objective to show a RR > 22%. Secondary objectives were toxicity, Progression-Free Survival (PFS), Overall Survival (OS), disease control rate (DCR) and RR according to Choi criteria.
45 patients met clinical inclusion criteria, and 41 were deemed treatable with SIRT after pretreatment angiography and included in the study. 34% of patients had abdominal extrahepatic lesions, 17% had thoracic lesions, tumor was unilobar in 66%, and median CA19.9 was 1499 UI/L. Grade 3 or more hematological toxicities were seen in 27 (66%) patients, and grade 3 or more non-hematological toxicities in 21 (49%). Median number of chemotherapy cycles were 6 (range 1-15). RECIST RR was 39% [90% CI: 26-53], and DCR was 98% (all 40 evaluable patients had disease control). In the 29 patients evaluated with Choi criteria, RR was 86%. 9 patients (22%) were downstaged to surgery, with 8 (20%) achieving R0 resection. Median PFS was 13 months [95% CI: 7-NR], with 12- and 24-months PFS rates of 51% and 37%, respectively. Median OS was 21 months [95% CI: 14-NR], with 12- and 24-months OS rates of 73% and 36%, respectively.
Combination of chemotherapy and SIRT achieved promising activity in first-line treatment of inoperable ICC, with median PFS and OS comparing favorably with chemotherapy-only historical data, and a significant proportion of patients downstaged to surgery. Toxicity was manageable. Further studies of SIRT in ICC are warranted.
Clinical trial identification
Legal entity responsible for the study
Centre Eugene Marquis, Rennes, France
J. Edeline: Consultant for BTG. E. Garin: Consultant for BTG. E. Boucher: Employee with BTG. All other authors have declared no conflicts of interest.