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Second- and third-line systemic therapy in patients with advanced esophagogastric cancer: a systematic review of the literature

ter Veer, E., Mohammad, N. H., Valkenhoef , van, G., Ngai, L. L., Mali, R. M. A., van Oijen, M. G. H. & van Laarhoven, H. W. M., Sep-2016, In : Cancer and metastasis reviews. 35, 3, p. 439-456 18 p.

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  • Emil ter Veer
  • Nadia Haj Mohammad
  • Gert Valkenhoef , van
  • Lok Lam Ngai
  • Rosa M. A. Mali
  • Martijn G. H. van Oijen
  • Hanneke W. M. van Laarhoven

The optimal second- and third-line chemotherapy and targeted therapy for patients with advanced esophagogastric cancer is still a matter of debate. Therefore, a literature search was carried out in Medline, EMBASE, CENTRAL, and oncology conferences until January 2016 for randomized controlled trials that compared second- or third-line therapy. We included 28 studies with 4810 patients. Second-line, single-agent taxane/irinotecan showed increased survival compared to best supportive care (BSC) (hazard ratio 0.65, 95 % confidence interval 0.53-0.79). Median survival gain ranged from 1.4 to 2.7 months among individual studies. Taxane- and irinotecan-based regimens showed equal survival benefit. Doublet chemotherapy taxane/irinotecan plus platinum and fluoropyrimidine was not different in survival, but showed increased toxicity vs. taxane/irinotecan monotherapy. Compared to BSC, second-line ramucirumab and second- or third-line everolimus and regorafenib showed limited median survival gain ranging from 1.1 to 1.4 months, and progression-free survival gain, ranging from 0.3 to 1.6 months. Third- or later-line apatinib showed increased survival benefit over BSC (HR 0.50, 0.32-0.79). Median survival gain ranged from 1.8 to 2.3 months. Compared to taxane-alone, survival was superior for second-line ramucirumab plus taxane (HR 0.81, 0.68-0.96), and olaparib plus taxane (HR 0.56, 0.35-0.87), with median survival gains of 2.2 and 4.8 months respectively. Targeted agents, either in monotherapy or combined with chemotherapy showed increased toxicity compared to BSC and chemotherapy-alone. This review indicates that, given the survival benefit in a phase III study setting, ramucirumab plus taxane is the preferred second-line treatment. Taxane or irinotecan monotherapy are alternatives, although the absolute survival benefit was limited. In third-line setting, apatinib monotherapy is preferred.

Original languageEnglish
Pages (from-to)439-456
Number of pages18
JournalCancer and metastasis reviews
Volume35
Issue number3
Publication statusPublished - Sep-2016

    Keywords

  • Advanced esophagogastric cancer, Chemotherapy, Targeted therapy, Second-line, Third-line, Meta-analysis, ADVANCED GASTRIC-CANCER, RANDOMIZED PHASE-II, ARBEITSGEMEINSCHAFT INTERNISTISCHE ONKOLOGIE, IRINOTECAN PLUS CISPLATIN, 2ND-LINE CHEMOTHERAPY, ESOPHAGEAL CANCER, SUPPORTIVE CARE, GASTROESOPHAGEAL JUNCTION, COMPARING IRINOTECAN, DOUBLE-BLIND

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