SIRT + chemo feasible, effective in unresectable intrahepatic cholangiocarcinoma

Selective internal radiation therapy (SIRT) with resin yttrium-90 microspheres followed by standard chemotherapy is feasible and effective in patients with unresectable intrahepatic cholangiocarcinoma (ICC), a phase II single-arm study in Hong Kong, Singapore and Thailand has shown.

The investigator-initiated, open-label trial included 24 patients (median age, 62 years; male, 62.5 percent; stage IVA/IVB disease, 75 percent; median diameter of largest tumour, 7.4 cm) recruited from the Prince of Wales Hospital in Hong Kong, the National Cancer Centre Singapore, the National University of Singapore’s Cancer Science Institute, and the Chulabhorn Hospital in Thailand. [Liver Cancer 2022;doi:10.1159/000525489]

“SIRT has a proven role in hepatocellular carcinoma [HCC], but clinical trial data are lacking on its role in ICC, especially in the context of standard chemotherapy,” said investigator Professor Simon Yu of the Department of Imaging and Interventional Radiology, Chinese University of Hong Kong (CUHK).

In the study, all patients were treated with SIRT (≥120 Gy to the intrahepatic tumour). Sixteen patients received subsequent standard chemotherapy with gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m²) on days 1 and 8 of a 21-day cycle (median, 5 cycles; median time from SIRT to chemotherapy commencement, 29 days). Eight patients were unable to receive chemotherapy due to disease progression (n=4), withdrawal of consent (n=2), or poor underlying medical conditions (n=2).

The primary endpoint of overall survival reached a median of 13.6 months in the intent-to-treat (ITT) population of 24 patients who received ≥1 cycle of SIRT, and was 21.6 months in the 16 patients who received ≥1 cycle of chemotherapy following SIRT. Median progression-free survival was 6.6 months and 9 months, respectively.

Overall response rate was 16.7 percent in the ITT population and 25 percent in patients who received chemotherapy following SIRT, while disease control rate was 58.3 percent and 75 percent, respectively.

Grade 3/4 treatment-related toxicities were observed in <10 percent of patients in the ITT population, with no safety signals observed.

During the SIRT phase, grade 3/4 toxicities included abdominal pain (n=1; 4 percent), vomiting (n=1; 4 percent), ascites (n=1; 4 percent), elevated aspartate transaminase (n=1; 4 percent), increased bilirubin (n=1; 4 percent), and hypercalcaemia (n=1; 4 percent).

“Two reasons may contribute to the low toxicity rate seen with SIRT in this clinical trial,” the investigators suggested. “First, during SIRT planning, we mandated lung shunting at a lower cut-off of 15 percent instead of 20 percent, which may prevent radiation-induced lung injury. Second, all four participating centres have extensive experience in SIRT administration to HCC.”

During the subsequent chemotherapy phase, common grade 3/4 toxicities were mainly myelosuppression, including neutropenia (n=4; 17 percent), anaemia (n=2; 8 percent), and thrombocytopenia (n=2; 8 percent).

“This is the first clinical trial evaluating serial combination of SIRT followed by standard gemcitabine plus cisplatin chemotherapy in ICC,” the investigators highlighted. “Our results suggest that this approach is feasible and effective in unresectable ICC. Further studies are required to study the optimal sequencing of SIRT and chemotherapy.”