Continuation of trastuzumab beyond progression in HER2-positive advanced esophagogastric cancer: a meta-analysis

Acta Oncol. 2018 Dec;57(12):1599-1604. doi: 10.1080/0284186X.2018.1503421. Epub 2018 Sep 28.

Abstract

Introduction: After progression on first-line trastuzumab-based therapy, no HER2-targeted agent is available for patients with HER2-positive esophagogastric cancer. However, continuation of trastuzumab after progression is an established strategy in HER2-positive breast cancer. We conducted a meta-analysis to investigate whether continuation of trastuzumab beyond first-line therapy in combination with chemotherapy is more effective compared to chemotherapy-alone.

Methods: PubMed, EMBASE, CENTRAL and meeting abstracts from ASCO and ESMO were searched up to June 2018 for studies (any design) investigating second-line trastuzumab plus chemotherapy compared to chemotherapy-alone for patients with HER2-positive esophagogastric cancer that progressed on first-line trastuzumab-based therapy. Meta-analysis was performed on the primary outcome, overall survival (OS), and on secondary outcomes progression-free survival (PFS), objective-response rate (ORR), and adverse events.

Results: Four cohort studies and one randomized controlled trial (RCT) were included with n = 200 patients who received second-line trastuzumab plus chemotherapy and n = 183 who received chemotherapy-alone. Meta-analysis showed that trastuzumab plus chemotherapy did not prolonged OS [HR = 0.72, 95% confidence interval (95% CI) = 0.47-1.08, p=.11). PFS was longer with trastzumab plus chemotherapy compared to chemotherapy-alone (HR = 0.64, 95% CI = 0.45-0.91, p<.05). There was no significant difference in ORR between the trastuzumab plus chemotherapy-group and the chemotherapy-alone group (ORR = 19.1% versus ORR = 13.4%, p=.13) and no significant differences in grade 3/4 and grade 1/2 adverse events.

Conclusions: This meta-analysis showed that patients who progressed on first-line trastuzumab-based therapy but of whom trastuzumab was continued in second-line and added to chemotherapy did not show longer OS or a higher ORR compared to patients receiving second-line chemotherapy-alone. However, PFS was prolonged and trastuzumab was not associated with additional safety concerns. In absence of available second-line HER2-targeted agents, a large prospective RCT should investigate if continuation of trastuzumab might be an attractive strategy, as this meta-analysis was mostly based on non-randomized studies and a RCT with a small sample size.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease Progression
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / pathology
  • Humans
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Trastuzumab / therapeutic use*

Substances

  • Trastuzumab