Real-world outcomes in circulating tumor DNA-detected isocitrate dehydrogenase 1-mutant cholangiocarcinoma: First-line gemcitabine and cisplatin with versus without immunotherapy.

Authors

Richard D Kim, Nikolas Naleid, Adrian Bubie, Nicole Zhang, Keelia Clemens

Published in

Cancer. Volume 132. Issue 20. Pages e70646. Oct 15, 2026.

Abstract

Comprehensive genomic profiling (CGP) is recommended for advanced cholangiocarcinoma (aCCA). Circulating tumor DNA (ctDNA) testing provides a noninvasive alternative with concordance to tissue. Standard first-line (1L) therapy is gemcitabine and cisplatin (GemCis) with or without immune checkpoint inhibitors (ICIs). Data suggest that patients with isocitrate dehydrogenase 1 (IDH1) mutations may derive less benefit from ICIs. This study evaluated outcomes with 1L GemCis versus GemCis + ICI in ctDNA-identified IDH1-mutant (IDH1+) aCCA.
Real-world data were analyzed from the InfinityAI Data Library, which links claims data with CGP results from Guardant360. Patients with IDH1+ aCCA identified between April 2019 and February 2025 who received 1L GemCis or GemCis + ICI were included. Outcomes were real-world time to next treatment (rwTTNT), real-world time to treatment discontinuation (rwTTD), and real-world overall survival (rwOS), compared via Kaplan-Meier estimates and log-rank tests.
Among 416 IDH1+ patients, 155 received GemCis and 113 received GemCis + ICI. No significant differences were observed in rwTTNT (hazard ratio [HR], 0.75; p = .13) or rwTTD (HR, 1.12; p = .40); however, rwOS was worse with GemCis + ICI compared with GemCis alone (16.0 months [95% CI, 13.6-19.9 months] vs. 30.0 months [95% CI, 24.1-41.0 months]; HR, 0.40; p < .001). In the GemCis + ICI aCCA cohort (N = 1150), IDH1+ patients (n = 113) had numerically shorter rwOS than non-IDH1+ patients (n = 1037) (HR, 0.75; p = .06).
In IDH1+ aCCA, addition of immunotherapy to GemCis was associated with inferior rwOS. These findings support obtaining ctDNA-based CGP before initiating 1L therapy, and underscore the need for prospective studies.

PMID:
42876026
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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