Ramucirumab in HER-2-positive gastroesophageal adenocarcinoma: an argument for overcoming trastuzumab resistance

Future Oncol. 2018 Feb;14(3):223-228. doi: 10.2217/fon-2017-0434. Epub 2018 Jan 10.

Abstract

Aim: Patients with advanced gastric cancer have a relatively poor prognosis with few therapeutic alternatives beyond first-line therapy. The purpose of this manuscript is to highlight the potential for prolonged responses in patients with HER-2-positive disease. Patients, materials & methods: We analyzed the data of patients diagnosed with HER-2-positive-advanced gastric cancer who progressed on trastuzumab-based combination therapy and subsequently received second-line therapy consisting of ramucirumab in combination with paclitaxel.

Results: Most patients had a stable disease after ramucirumab-based therapy (50%, 5/10), median duration to disease control was 8 months.

Conclusion: The prolonged duration of response that we observed indicates that an interaction between the EGF pathway and the angiogenesis pathway requires further clinical investigations.

Keywords: HER-2; VEGF; VEGF-R2; advanced gastric cancer; angiogenesis; crosstalk; gastroesophageal cancer; ramucirumab; second-line therapy; trastuzumab.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Drug Resistance, Neoplasm
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Ramucirumab
  • Receptor, ErbB-2 / genetics
  • Retreatment
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Trastuzumab / therapeutic use
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab