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- Title
Continuation of trastuzumab beyond progression in HER2-positive advanced esophagogastric cancer: a meta-analysis.
- Authors
ter Veer, Emil; van den Ende, Tom; Creemers, Aafke; de Waal, Laura; van Oijen, Martijn G. H.; van Laarhoven, Hanneke W. M.
- 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.
- Subjects
TRASTUZUMAB; CANCER chemotherapy; COMBINATION drug therapy; CONFIDENCE intervals; EPIDERMAL growth factor; ESOPHAGEAL tumors; EXPERIMENTAL design; MEDICAL information storage &; retrieval systems; MEDLINE; META-analysis; METASTASIS; ONLINE information services; TUMOR classification; SYSTEMATIC reviews; SAMPLE size (Statistics); RANDOMIZED controlled trials; TREATMENT effectiveness; ADVERSE health care events; ODDS ratio; PROGNOSIS; THERAPEUTICS
- Publication
Acta Oncologica, 2018, Vol 57, Issue 12, p1599
- ISSN
0284-186X
- Publication type
Article
- DOI
10.1080/0284186X.2018.1503421