The Role of Radioembolization in First-Line iCCA

Liver-directed therapies for first-line treatment of intrahepatic cholangiocarcinoma (iCCA) include transarterial radioembolization (also known as selective internal radiation therapy [SIRT]), transarterial chemoembolization (TACE), hepatic artery infusion (HAI), liver transplant, and external beam radiotherapy (EBRT). At the 5th annual CCA Summit meeting, Amit Mahipal, MBBS, MPH, discussed the evolving role of radioembolization in first-line iCCA.¹

Systemic therapies including the gemcitabine/cisplatin plus paclitaxel regimen (median overall survival [OS], 19.2 months)² and the durvalumab plus gemcitabine/cisplatin regimen (median OS, 12.8 months)³ have demonstrated better outcomes compared to the historical control of gemcitabine/cisplatin alone in the ABC-02 trial (median OS, 11.7 months).⁴

The randomized multicenter SIRFLOX trial showed that the addition of SIRT using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)–based chemotherapy in patients with liver-dominant or liver-only previously untreated metastatic colorectal cancer did not improve progression-free survival (PFS) at any site but significantly delayed disease progression in the liver.⁵

The MISPHEC study demonstrated that the combination of SIRT with gemcitabine/cisplatin was feasible in first-line treatment of patients with advanced CCA; a response rate of 39% was achieved, whereas median PFS was 14 months, and median OS was 22 months.⁶ Although downstaging led to resection in 22% of the patients in the study, this can also be achieved with systemic therapy alone.^1,6 These results are impressive; however, this was a highly selected patient population and confirmation in larger trials is needed.¹

HAI plus systemic chemotherapy was found to be highly active and tolerable in patients with unresectable iCCA; partial radiographic response was achieved in 58% of patients, and disease control at 6 months occurred in 84% of patients; median PFS was 11.8 months, and median OS was 25 months.⁷ A systematic review and meta-analysis of locoregional treatments showed a pooled mean OS of <24 months for EBRT, SIRT, TACE, and HAI, which was comparable to those achieved with systemic therapy.⁸

Dr Mahipal concluded that liver-directed therapies have shown promise in CCA and may be used as adjunct to systemic therapy; however, the available evidence does not support their role in CCA.¹ He noted liver-directed therapies lack standardization and require careful patient selection and institutional experience. Larger multi-institutional trials are warranted to establish liver-directed therapies as standard of care. He recommended that next-generation sequencing should be done in all patients prior to making treatment decisions to exclude patients with FGFR fusion or microsatellite instability-high disease, who may benefit from more targeted therapies.

Sources:

1. Mahipal A. The role of radioembolization on first-line iCCA. Presented at: 5th Annual CCA Summit Meeting, October 19-21, 2023; Scottsdale, AZ.
2. Shroff RT, Javle MM, Xiao L, et al. Gemcitabine, cisplatin, and nab-paclitaxel for the treatment of advanced biliary tract cancers: a phase 2 clinical trial. JAMA Oncol. 2019;5(6):824-830.
3. Oh D-Y, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):1-11.
4. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273-1281.
5. van Hazel GA, Heinemann V, Sharma N, et al. SIRFLOX: randomized phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol 2016;34:1723-1731.
6. Edeline J, Touchefeu Y, Guiu B, et al. Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2020;6(1):51-59.
7. Cercek A, Boerner T, Tan BR, et al. Assessment of hepatic arterial infusion of floxuridine in combination with systemic gemcitabine and oxaliplatin in patients with unresectable intrahepatic cholangiocarcinoma. JAMA Oncol. 2020;6(1):60-67.
8. Edeline J, Lamarca A, McNamara MG, et al. Locoregional therapies in patients with intrahepatic cholangiocarcinoma: a systematic review and pooled analysis. Cancer Treat Rev. 2021;99:102258.