Z Gastroenterol 2025; 63(08): e548-e549
DOI: 10.1055/s-0045-1810972
Abstracts | DGVS/DGAV
Kurzvorträge
Innovative diagnostische & therapeutische Optionen bei pankreatikobiliären Karzinomen Donnerstag, 18. September 2025, 14:15 – 15:43, Seminarraum 6 + 7

Analysis of clinically actionable alterations in baseline tumor versus plasma samples in participants of the TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer

U Pelzer
1   Sana Klinikum Lichtenberg, Division for Internal Medicine IV: Hematology, Oncology, Palliative Care, Berlin, Deutschland
,
D-Y Oh
2   Seoul National University Hospital, Division of Medical Oncology, Department of Internal Medicine; Seoul National University College of Medicine, Cancer Research Institute, Seoul, Korea, Republik
,
S Qin
3   Jinling Hospital, Cancer Center of Nanjing, Nanjing, China
,
L Antonuzzo
4   Careggi University Hospital, Clinical Oncology Unit; University of Florence, Department of Experimental and Clinical Medicine, Florence, Italien
,
D Tougeron
5   Poitiers University Hospital, Department of Gastroenterology and Hepatology, Poitiers, Frankreich
,
C-K Lee
6   Yonsei University College of Medicine, Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Seoul, Korea, Republik
,
B Tan
7   Washington University School of Medicine, Department of Medicine, St. Louis, MO, Vereinigte Staaten
,
M Ikeda
8   National Cancer Center Hospital East, Department of Hepatobiliary and Pancreatic Oncology, Kashiwa, Japan
,
J Wang
9   AstraZeneca, Oncology R&D, Late-stage Development, New York, NY, Vereinigte Staaten
,
H-Y Lin
10   AstraZeneca, Oncology Data Science, Waltham, MA, Vereinigte Staaten
,
Y Lee
11   AstraZeneca, Translational Medicine, Oncology R&D, Gaithersburg, MD, Vereinigte Staaten
,
P McCoon
12   AstraZeneca, Translational Medicine, Oncology R&D, Waltham, MA, Vereinigte Staaten
,
J W Valle
13   University of Manchester, Cholangiocarcinoma Foundation, Herriman, UT, USA and Division of Cancer Sciences, Manchester, Vereinigtes Königreich
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    Background: In the TOPAZ-1 study (NCT03875235), durvalumab combined with gemcitabine and cisplatin (D+GC) significantly improved overall survival (OS) in advanced biliary tract cancer patients compared to placebo with GC (P+GC). Updated results show a meaningful 3-year OS benefit for D+GC.

    Objective: This exploratory analysis tested circulating tumor DNA (ctDNA) in plasma samples for blood-based detection of clinically actionable alterations (CAAs) and investigated the potential of this method to guide treatment decisions.

    Methods: Baseline genomic alterations were retrospectively evaluated in tumor samples (FMI biomarker evaluable population [BEP], n=441) and plasma samples (GH BEP, n=643) using FoundationOne (Foundation Medicine Inc., Cambridge, MA) and Guardant INFINITY™ (Guardant Health, Redwood City, CA) assays, respectively. Mutation prevalence and outcome associations were compared in the FMI BEP and GH BEP. The agreement of CAAs detected in tumor versus ctDNA were assessed in 419 pts with both sample types (FMI-GH BEP).

    Results: The FMI BEP and GH BEP represented 64% and 94% of the TOPAZ-1 final analysis set (685 pts), respectively. The relative prevalence and overall mutational landscape detected in plasma ctDNA was consistent with that observed by tumor profiling, with the notable exception that genes harboring complex alterations were less frequently detected in ctDNA (e.g. ERBB2, FGFR2, CKDN2A/2B/MTAP). The most common alterations (>15% prevalence in both BEPs) observed were in TP53 (49%/52%), KRAS (24%/17%), and ARID1A (21%/16%) (in the FMI/GH BEPs, respectively). The relative prevalence of alterations within geographic and anatomic subgroups was similar in tumor versus plasma for most CAAs. The overall percent agreement in CAAs was≥93%, and negative percent agreement was≥97%. However, positive percent agreement was notably low for ERBB2 amplification (52%) and FGFR2 fusions (47%). OS hazard ratios for D+GC versus P+GC in the GH BEP were<1 for both CAAs and wild-type, except for ERBB2 amplification.

    Conclusions: The FoundationOne tumor assay and Guardant INFINITY™ ctDNA assay showed similar concordance and prevalence for simple mutations, suggesting that plasma ctDNA testing has potential utility in clinical practice. However, negative status by ctDNA for the complex alterations found in FGFR2 and ERBB2 would require further testing of tumors.

    Previously presented at ASCO GI 2025, Abstract 625, Do-Youn Oh et al. – Reused with permission.


     

    Publication History

    Article published online:
    04 September 2025

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