First-Line Radioembolization in iCCA

Management of patients with intrahepatic cholangiocarcinoma (iCCA) poses a clinical challenge since the majority of patients are diagnosed with locally advanced, unresectable disease, and treatment options are limited to systemic and local regional therapies. At the 5th annual CCA Summit meeting, Sarah White, MD, MS, FSIR, FCIRSE, presented clinical data supporting the clinical benefit of radioembolization in cholangiocarcinoma (CCA).¹

In the first-line setting, the ABC-02 trial established gemcitabine/cisplatin as the standard first-line systemic therapy option for patients with iCCA (median overall survival [OS], 11.7 months; median progression-free survival [PFS], 8 months).² The gemcitabine/cisplatin platform was further reinforced with addition of paclitaxel in the single-arm phase 2 GAP trial (median OS, 19.2 months; median PFS, 11.8 months)³; and the addition of durvalumab to the gemcitabine/cisplatin platform in the TOPAZ-1 trial is another effective regimen (median OS, 12.8 months; PFS, 7.2 months).⁴ In the second-line setting following progression on gemcitabine/cisplatin, the ABC-06 trial showed that the addition of FOLFOX to active symptom control had limited efficacy (median OS, 6.2 months; PFS, 4.0 months).⁵

Treatment outcomes after yttrium-90 (90Y) radioembolization in patients with unresectable iCCA were better than those reported with systemic therapy.¹ Buettner and colleagues reported that 90Y radioembolization resulted in median OS from diagnosis of 29 months and median OS from intra-arterial therapy of 11 months.⁶ The phase 2, prospective, open-label, multicenter MISPHEC study demonstrated that the combination of 90Y plus systemic therapy as first-line therapy for patients with advanced CCA yielded a response rate of 39%; median PFS was 14 months, and median OS was 22 months; and downstaging led to resection in 22% of patients.⁷ In the MISPHEC study, the frequency of treatment-related adverse events was similar to that reported in the ABC-02 trial (71% vs 70.7%, respectively).^1,2,7 In another study, a subgroup of patients with iCCA who received first-line 90Y transarterial radioembolization with resin microspheres showed a median OS of 22 months versus 9 months in the group that received subsequent 90Y TARE; median PFS of 7.4 months versus 2.7 months, respectively; and median time to progression of 13 months versus 3 months, respectively.⁸ Moreover, 52% of patients went on to surgical resection.⁸

Dr White concluded that the growing body of evidence supports the use of radioembolization in clinical practice based on data showing that addition of locoregional therapy prolongs survival and can downstage select patients to curative resection, particularly in conjunction with chemotherapy. However, further trials are needed to understand optimal timing of combination therapies.¹

Sources:

1. White S. Cholangiocarcinoma: radioembolization in first line. Presented at: 5th Annual CCA Summit Meeting, October 19-21, 2023; Scottsdale, AZ.
2. 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.
3. 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.
4. 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.
5. Lamarca A, Palmer DH, Wasan HS, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021;22(5):P690-P701.
6. Buettner S, Braat AJAT, Margonis GA, et al. Yttrium-90 radioembolization in intrahepatic cholangiocarcinoma: a multicenter retrospective analysis. J Vasc Interv Radiol. 2020;31:1035-1043.
7. 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.
8. Sarwar A, Ali A, Ljuboja D, et al. Neoadjuvant yttrium-90 transarterial radioembolization with resin microspheres prescribed using the medical internal radiation dose model for intrahepatic cholangiocarcinoma. J Vasc Interv Radiol. 2021;32:1560-1568.