Systemic therapy beyond first-line in advanced gastric cancer: An overview of the main randomized clinical trials

Crit Rev Oncol Hematol. 2016 Mar:99:1-12. doi: 10.1016/j.critrevonc.2015.09.004. Epub 2015 Nov 30.

Abstract

Following progression on first-line platinum and fluoropyrimidine-based chemotherapy, prognosis for advanced gastric cancer patients is extremely poor. Thus, new and effective treatments are required. Based on positive results of recent randomized controlled trials, second-line monochemotherapies with either irinotecan or taxanes confer a median overall survival of approximately 5 months in gastro-esophageal and gastric adenocarcinoma. Combination of weekly paclitaxel and ramucirumab, a novel anti-angiogenic VEGFR2 antibody, pushes the overall survival up to over 9.5 months, whereas apatinib, a novel oral VEGFR2 tyrosine kinase inhibitor, seems to be promising in heavily pretreated patients. In contrast, the role of EGFR/HER2 and mTOR inhibitors is controversial. Studies are heterogeneous for tumor population, geographical areas, quality of life assessment, type of first-line therapy and response to that, making clinical practice application of the trial results difficult. Furthermore, sustainability is challenging due to high cost of novel biotherapies.

Keywords: Advanced gastric cancer; Molecular targeted agents; Randomized controlled trials; Second-line chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant / methods*
  • Chemotherapy, Adjuvant / standards
  • Chemotherapy, Adjuvant / statistics & numerical data
  • Disease Progression
  • Humans
  • Neoadjuvant Therapy
  • Paclitaxel / administration & dosage
  • Quality of Life
  • Randomized Controlled Trials as Topic* / standards
  • Randomized Controlled Trials as Topic* / statistics & numerical data
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Paclitaxel