Abstract
Purpose
Trastuzumab plus chemotherapy is an effective therapy in HER2 positive advanced gastric cancer (AGC). However, the optimal maintenance treatment in patients benefited from the first line therapy remains unclear.
Methods
In this prospective observational study, patients with HER2 positive AGC who received six cycles of trastuzumab-based first line chemotherapy were divided into two arms according to the maintenance strategy: trastuzumab monotherapy (arm A) and trastuzumab plus mono-chemo-agent derived from the initial chemotherapy (arm B). The primary end point was overall survival (OS), the secondary end points were first line progression free survival (PFS), maintenance PFS, cost-effectiveness ratios (CERs), incremental cost-effectiveness ratios (ICERs) and safety.
Results
30 patients were in arm A received trastuzumab monotherapy and 48 were in arm B. The clinical and pathological characteristics of two arms were well balanced. There was no significant difference of median OS (16.5 vs 20.0 months, HR 0.71 P = 0.169) or PFS (7.9 vs 11.0, HR 1.06, P = 0.892) between two arms, however, adding chemo-agent could lead to a 29% reduction in mortality risk. Adverse effects including cardiac safety were also similar. Subgroup analysis showed chemotherapy additional to trastuzumab benefited on OS in patients who had stable disease (SD) of response (HR: 0.084, P = 0.004), elder than 65 years old (HR: 0.4, P = 0.015), without liver metastasis (HR: 0.271, P = 0.008) or less than two organs of distance metastasis (HR: 0.263, P = 0.005). The average cost per patients in arm A was 153,137 RMB and 165,195 RMB in arm B. While, ICER in arm A was 1.29 times higher than arm B (CERs of two arms were 19,384 vs 15,018 RMB).
Conclusion
Mono-chemo-agent combined with trastuzumab showed an advantage of absolute value and hazard ratio on OS, in addition to ICER of PFS for patients who benefit from the initial six cycles of trastuzumab-based first line therapy, especially in patients with certain clinical or treatment-related characterisitics. A large sample randomized trial is warranted.
Similar content being viewed by others
References
Bang YJ et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376:687–697. https://doi.org/10.1016/s0140-6736(10)61121-x
Chen W et al (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66:115–132. https://doi.org/10.3322/caac.21338
Cohn DE, Kim KH, Resnick KE, O’Malley DM, Straughn JM Jr (2011) At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol 29:1247–1251. https://doi.org/10.1200/JCO.2010.32.1075
Dulak AM et al (2012) Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res 72:4383–4393. https://doi.org/10.1158/0008-5472.can-11-3893
Gomez-Martin C et al (2012) HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer. J Clin Pathol 65:751–757. https://doi.org/10.1136/jclinpath-2012-200774
Gomez-Martin C et al (2014) A critical review of HER2-positive gastric cancer evaluation and treatment: from trastuzumab, and beyond. Cancer Lett 351:30–40. https://doi.org/10.1016/j.canlet.2014.05.019
Gong J et al (2016) Optimal regimen of trastuzumab in combination with oxaliplatin/capecitabine in first-line treatment of HER2-positive advanced gastric cancer (CGOG1001): a multicenter, phase II trial. BMC Cancer 16:68. https://doi.org/10.1186/s12885-016-2092-9
Gravalos C et al (2011) Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer. Clin Transl Oncol 13:179–184. https://doi.org/10.1007/s12094-011-0637-6
Halon A, Donizy P, Biecek P, Rudno-Rudzinska J, Kielan W, Matkowski R (2012) HER-2 expression in immunohistochemistry has no prognostic significance in gastric cancer patients. Sci World J 2012:941259. https://doi.org/10.1100/2012/941259
Hegewisch-Becker S et al (2015) Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 16:1355–1369. https://doi.org/10.1016/s1470-2045(15)00042-x
Kimura Y et al (2018) Correction to: Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC06). Gastric Cancer 21:428. https://doi.org/10.1007/s10120-017-0784-8
Kurokawa Y et al (2014) Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1). Br J Cancer 110:1163–1168. https://doi.org/10.1038/bjc.2014.18
Luo HY et al (2016) Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety. Ann Oncol 27:1074–1081. https://doi.org/10.1093/annonc/mdw101
Markman M et al (2003) Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol 21:2460–2465. https://doi.org/10.1200/jco.2003.07.013
Perren TJ et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484–2496. https://doi.org/10.1056/nejmoa1103799
Ryu MH et al (2015) Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer. Eur J Cancer 51:482–488. https://doi.org/10.1016/j.ejca.2014.12.015
Shah MA et al (2017) HELOISE: phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 35:2558–2567. https://doi.org/10.1200/jco.2016.71.6852
Siegel RL, Miller KD, Jemal A (2019) Cancer statistics. CA Cancer J Clin 69:7–34. https://doi.org/10.3322/caac.21551
Smith HJ, Walters Haygood CL, Arend RC, Leath CA 3rd, Straughn JM Jr (2015) PARP inhibitor maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer: a cost-effectiveness analysis. Gynecol Oncol 139:59–62. https://doi.org/10.1016/j.ygyno.2015.08.013
Tabernero J et al (2018) Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol 19:1372–1384. https://doi.org/10.1016/s1470-2045(18)30481-9
Ter Veer E, van den Ende T, Creemers A, de Waal L, van Oijen MGH, van Laarhoven HWM (2018) Continuation of trastuzumab beyond progression in HER2-positive advanced esophagogastric cancer: a meta-analysis. Acta Oncol 57:1599–1604. https://doi.org/10.1080/0284186x.2018.1503421
Thuss-Patience PC et al (2017) Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol 18:640–653. https://doi.org/10.1016/s1470-2045(17)30111-0
Zhu B, Wu JR, Zhou XP (2015) A Retrospective Comparison of Trastuzumab Plus Cisplatin and Trastuzumab Plus Capecitabine in Elderly HER2-Positive Advanced Gastric Cancer Patients. Medicine (Baltimore) 94:e1428. https://doi.org/10.1097/md.0000000000001428
Funding
This research is supported by the Shanghai Science and Technology Commission (17411951400)
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All other authors report no relevant conflict of interest.
Ethical approval
This study was approved by the Research Ethics Committees of Zhongshan hospital, Fudan University. The study was performed in accordance with the 1964 Declaration of Helsinki and its later amendments and Good Clinical Practice guidelines.
Informed consent
All patients signed written informed consents in our study
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Li, Q., Lv, M., Jiang, H. et al. A prospective observational study on the optimal maintenance strategy in HER2-positive advanced gastric cancer treated with trastuzumab-based therapy. J Cancer Res Clin Oncol 146, 287–295 (2020). https://doi.org/10.1007/s00432-019-03060-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-019-03060-5