Meeting
2024 ASCO Gastrointestinal Cancers Symposium
Characterizing outcomes of ERBB2-amplified biliary tract cancer.
Authors
Daniel Aaron Fox
Baylor College of Medicine, Houston, TX
Daniel Aaron Fox , Jaime Haro-Silerio , Deepak Bhamidipati , Funda Meric-Bernstam , Shubham Pant , Jeffrey S. Ross , Zishuo Ian Hu , Eugene Jon Koay , Ethan B. Ludmir , Hop Sanderson Tran Cao , Ching-Wei D. Tzeng , Yun Shin Chun , Jean-Nicolas Vauthey , Timothy E. Newhook , Zeyad Metwalli , Peiman Habibollahi , Veronica L. Cox , Hyunseon Kang , Milind M. Javle , Sunyoung S. Lee
Organizations
Baylor College of Medicine, Houston, TX, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Foundation Medicine, Inc., Cambridge, MA, Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Funding
No funding sources reported
Background: A subset of biliary tract cancers (BTC) feature amplification (amp) of the human epidermal growth factor receptor 2 (ERBB2) gene. The prognostic role and treatment in these patients (pts) are poorly understood. This study aims to characterize the clinical outcomes and molecular profiles of ERBB2-amp BTC. Methods: We conducted a retrospective analysis of clinical outcomes data and next-generation sequencing (NGS) at MD Anderson (MDA) and Foundation Medicine (FMI) from 2009-2023 in pts with ERBB2-amp BTC including all classes of genomic alterations (GA) in other genes. Progression-free survival (PFS) and overall survival (OS) were assessed by the log-rank test. Results: 80 pts (MDA) were identified with ERBB2-amp BTC with documented treatment and NGS data. Pts (Table) who received ERBB2-directed therapy (22.4 vs. 12.0 m, p=0.004), surgery (21.0 vs. 12.0 m, p=0.002), local therapy with RT/ablation/Y90 (excluding surgical pts, 20.6 vs. 11.6 m, p = 0.0001) had significantly longer OS. Median PFS (mPFS) without ERBB2-directed therapy for 1st, 2nd, and 3rd line systemic therapy was 4.1, 3, and 2.2 m. mPFS with all ERBB2-directed therapy was 4.1 m, but that of gemcitabine (gem)-based plus trastuzumab (tt) and 5FU-based plus tt was 7.8 and 3.8 m (p=0.018). The most common concurrent-GA at MDA, any co-amps (72.7%; 19.2 vs. 20.3 m, p=0.69) and TP53 inactivating mutation (70.4%; 16.6 vs. 14.9 m, p=0.89), had no OS association; 3rd most common co-GA found, CDK12 amp (46.4%), had a trend toward a better OS (19.2 vs. 14.3 m, p=0.089). FMI database showed ERBB2 amp in 3.2%, 5.4%, and 8.9% in intrahepatic cholangiocarcinoma (iCCA), extrahepatic CCA, and gallbladder cancer. The most common co-GA included TP53, CDKN2A/B, and CCNE1. FGFR2 fusions (iCCA) were mutually exclusive with ERBB2 amp (0%, MDA/FMI); IDH1 (iCCA) with ERBB2 amp, 5.7 and 4.3% (MDA and FMI). Conclusions:ERBB2-amp BTC has shorter mPFS or mOS without ERBB2-directed therapy, surgery, or local therapy, suggesting clinical benefit from multi-disciplinary care and targeted therapy. Co-GA with ERBB2-amp did not demonstrate a significant association with survival outcomes.
| OS all patients | 16.1 m | |
|---|---|---|
| PFS, chemo | 1st line gem-based vs. 5FU-based | 4.2 vs. 4.1 m (p=0.70) |
| 2nd line gem-based vs. 5FU-based | 3.0 vs 3.2 m (p=0.89) | |
| MDA (80) DNA co-GA | Any co-amp(s) (72.7%), TP53 (70.4%), CDK12 amp (45.4%), CCNE1 amp (17.0%), CDKN2A/B (15.9%), KRAS (11.4%), ATM (11.2%), other ERBB2 GA (9.1%) | |
| FMI DNA co-GA | iCCA (7,963) | TP53 (74.8%), CDKN2A (34%), CDKN2B (19.1%), TERT (19%), SMAD4 (12.4%), CCNE1 amp (12.1%), MYC amp (11.7%), KRAS mutation/amp (4.6/2.5%) |
| eCCA (1,285) | TP53 (85.3%), CDKN2A (37.3%), CDKN2B (21.3%), SMAD4 (20%), MTAP loss (14.8%), KRAS mutation (14.7%), RBM10 (11.3%), and ERBB3 (10.7%) | |
| Gallbladder (3,837) | TP53 (89.6%), CDKN2A (30.4%), CCNE1 amp (21.4%), CDKN2B (19.1%), SMAD4 (15%), CDK12 rearrangement (12.4%), MTAP loss (11.3%) | |
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Track
Pancreatic Cancer,Hepatobiliary Cancer,Neuroendocrine/Carcinoid,Small Bowel Cancer
Sub Track
Therapeutics
Citation
J Clin Oncol 42, 2024 (suppl 3; abstr 492)
DOI
10.1200/JCO.2024.42.3_suppl.492
Abstract #
492
Poster Bd #
C17
Abstract Disclosures
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