HER2-Positive Esophagogastric Cancer — TRAP Trial (MSK, Cancer Cell Reports 2023)

Overview

Integrated dataset from a Phase II clinical trial (NCT02954536) and a retrospective cohort of HER2-positive metastatic esophagogastric cancer (EGC) patients at MSK, supporting analyses of HER2 IHC uniformity, ctDNA dynamics, and immunotherapy response. Data deposited in cBioPortal as egc_trap_ccr_msk_2023. PMID:37406106

Composition

  • Phase II trial cohort: 37 patients with HER2-positive (IHC 3+ or IHC 2+/FISH+) metastatic esophagogastric, gastroesophageal junction, or gastric adenocarcinoma treated with pembrolizumab, trastuzumab, capecitabine, and oxaliplatin. PMID:37406106
  • MSK retrospective cohort: 226 patients with HER2-positive EGC who received platinum-based chemotherapy with HER2-directed therapy from 2010 to 2022. PMID:37406106
  • scRNA-seq cohort: Paired pre- and on-treatment biopsies from 7 patients (3 with CAPOX + trastuzumab, 4 without). PMID:37406106
  • Cancer types: esophageal (ESCA), gastroesophageal junction (GEJ), and gastric (STAD) adenocarcinoma. PMID:37406106

Assays / panels (linked)

Papers using this cohort

  • PMID:37406106 — Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer.

Notable findings derived from this cohort

  • Median PFS 13 months, median OS 27 months, ORR 89% in the Phase II trial (n=37). PMID:37406106
  • Uniform HER2 IHC 3+ predicted longer median PFS (15 vs. 8.5 months, P=0.004). PMID:37406106
  • ctDNA clearance by 9 weeks associated with longer PFS (HR 0.18, P=0.001). PMID:37406106
  • Resistance mechanisms upon progression included PIK3CA, KRAS, MET, and EGFR alterations; loss of HER2 expression in 48%. PMID:37406106
  • Multivariable model: ERBB2 amplification was a positive prognostic factor; MYC and CDKN2A/B alterations were negative prognostic factors. PMID:37406106

Sources

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