Post-hoc Analysis of the ABC-01, -02, and -03 Trials in Patients With Advanced eCCA

This post-hoc analysis of the ABC-01, -02, and -03 clinical trials provides reference survival data for patients with advanced extrahepatic cholangiocarcinoma treated with first-line gemcitabine/cisplatin chemotherapy.

Earlier data showed that patients with intrahepatic cholangiocarcinoma (iCCA) have a better prognosis compared with other biliary tract cancers¹; however, information is limited regarding outcomes for patients with extrahepatic cholangiocarcinoma (eCCA). At the 2023 ESMO Congress in Madrid, Spain, Angela Lamarca, MD, PhD, MSC, presented findings from a post-hoc analysis of reference survival data for patients with advanced eCCA treated with first-line gemcitabine/cisplatin (GemCis) chemotherapy within the prospective, randomized ABC-01, -02, and -03 studies.²

A total of 534 patients were enrolled in the ABC-01, -02, and -03 studies, and 179 (56.29%) had eCCA (107 distal CCA [dCCA], 72 hilar CCA [hCCA]).² Of these patients, 117 were treated with GemCis and were eligible for analysis.² Most patients (82 [70.1%]) had metastatic disease at the time of recruitment.² Objective radiological response was achieved in 28 (23.93%) patients with eCCA: 19 (27.94%) with dCCA, and 9 (18.37%) with hCCA.² The median progression-free survival (PFS) for patients with eCCA, dCCA, and hCCA was 8.37 months (95% confidence interval [CI], 7.36-9.33), 8.28 months (95% CI, 6.31-9.39), and 8.37 months (95% CI, 6.53-10.61), respectively; median overall survival (OS) was 12.76 months (95% CI, 10.44-16.12), 14.25 months (95% CI, 8.80-17.44), and 12.18 months (95% CI, 8.31-16.12), respectively.² Patients with eCCA with locally advanced disease had a longer median PFS (13.1 months; 95% CI, 8.8-16.6) and OS (17.4 months; 95% CI, 14.3-21.1) compared with patients with advanced eCCA (PFS, 8.37 months [95% CI, 7.36-9.33]; OS, 12.76 months [95% CI, 10.44-16.12]), dCCA (PFS, 8.28 [95% CI, 6.31-9.39]; OS, 14.25 [95% CI, 8.80-17.44]), and hCCA (PFS, 8.37 [95% CI, 6.53-10.61]; OS, 12.18 [95% CI, 8.31-16.12]).² Multivariable survival analysis for PFS confirmed worse PFS for patients with eCCA who had a performance status of 1/2 versus 0 (hazard ratio [HR], 13.24; 95% CI, 2.09-83.49) and high baseline CA 125 (HR, 1.0001; 95% CI, 1.0004-1.01; P=.002) when adjusted for other prognostic factors identified in the univariate analysis (stage, Ca 19-9).² These remained significant when adjusted for site of eCCA.²

Lamarca and colleagues determined in this post-hoc analysis that patient outcomes were similar regardless of location of eCCA, but outcomes were worse than those reported historically for iCCA, specifically for OS.² Survival in eCCA was strongly correlated with performance status and baseline tumor markers (CA 125).² Future studies should focus on outcomes with first-line GemCis combined with immunotherapy.²

References

1. Lamarca A, Ross P, Wasan HS, et al. Advanced intrahepatic cholangiocarcinoma: post hoc analysis of the ABC-01, -02, and -03 clinical trials. J Natl Cancer Inst. 2020;112(2):200-210.
2. Lamarca A, Ross P, Wasan HS, et al. Advanced extrahepatic cholangiocarcinoma: post-hoc analysis of the ABC-01, -02 and -03 clinical trials. Presented at: ESMO Congress 2023, October 20-24, 2023; Madrid, Spain.