Clinical Outcomes and ctDNA Correlates for CAPOX BETR: A phase II trial of Capecitabine, Oxaliplatin, Bevacizumab, Trastuzumab in Previously Untreated Advanced HER2+ Gastroesophageal Adenocarcinoma

We performed circulating tumor DNA (ctDNA) analysis on plasma of patients with advanced HER2 positive gastroesophageal adenocarcinomas who were treated on a phase 2 clinical trial testing the addition of bevacizumab to capecitabine, oxaliplatin, and trastuzumab. ctDNA was analyzed using panel based next generation sequencing assay (Predicine CARE), low-pass whole genome sequencing (LP-WGS), and methylation based panel assay (Predicine ALERT). This allowed us to derive tumor mutational profiles, circulating tumor fractions in plasma, and changes in both over time. We show that tumor fraction and the presence of mutations in the MAPK pathway are prognostic in our patient cohort. LP-WGS data from baseline and cycle 2 of treatment is available through dbGaP. Additional data is submitted alongside the manuscript.

• Study Design:
  • Clinical Trial
• Study Type:
  • Clinical Trial
• Total number of consented subjects: 30
• Subject Sample Telemetry Report (SSTR)

• BioProject
• MeSH
• Gene
• Clinical Trials
  • NCT01191697

Inclusion:

1. Histologically confirmed newly diagnosed metastatic or locally advanced unresectable, HER2-positive adenocarcinoma of the esophagus, gastroesophageal junction, or stomach.
2. Required to have measurable disease, defined by RECIST 1.1
3. ECOG performance status < 2
4. Adequate organ and bone marrow function.
5. Patients were required to have LVEF > 50% as determined by MUGA scan or echocardiogram.

Exclusion:

1. Active brain or CNS metastases
2. Known dihydropyrimidine dehydrogenase deficiency
3. Uncontrolled hypertension, history of CVA, TIA, MI or unstable angina in the past 6 months
4. Evidence of bleeding diathesis or coagulopathy
5. Patients with serious, unhealed wounds, bone fractures, skin ulcers, > grade 1 peripheral neuropathy
6. Known to be seropositive for HIV, Hepatitis B or C
7. Lacking physical integrity of the upper gastrointestinal tract or having a malabsorption syndrome

• Primary Phenotype: Esophageal Neoplasms
• Stomach Neoplasms
• Receptor, ErbB-2
• Trastuzumab
• Bevacizumab

• ERBB2

• Principal Investigators
  • Harshabad Singh, MBBS. Dana-Farber Cancer Institute, Boston, MA, USA.
  • Peter C. Enzinger, MD. Dana-Farber Cancer Institute, Boston, MA, USA.
• Funding source
  • Funded by Genentech. South San Francisco, CA, USA.