Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

Daniel V. Catenacci, Joseph Chao, Kei Muro, Salah Eddin Al-Batran, Samuel J. Klempner, Zev A. Wainberg, Manish A. Shah, Sun Young Rha, Atsushi Ohtsu, Astra M. Liepa, Holly Knoderer, Anindya Chatterjee, Eric Van Cutsem

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Background: Platinum and fluoropyrimidine combinations typically comprise first-line (1L) therapy in advanced gastric cancer or gastroesophageal junction adenocarcinoma (G/GEA), although controversy exists regarding the use of 5doublet versus triplet cytotoxic regimens. Historically, second-line (2L) and third-line or later (3L+) therapy has been fragmented. Recent trials have increased the need for optimal treatment sequencing in advanced G/GEA. Materials and Methods: We conducted a systematic search of peer-reviewed manuscripts of randomized clinical trials examining 1L, 2L, and 3L+ therapy for advanced G/GEA published from 2009 through November 19, 2019. When available, overall survival, progression-free survival, time to progression, overall response rate, and toxicity were extracted from each and compared descriptively. Results: In 1L therapy, chemotherapy triplets demonstrated variable efficacy improvements with invariable increased toxicity compared with platinum/fluoropyrimidine doublets. Currently, the only published report of positive outcomes using biologics in 1L describes adding trastuzumab in HER2-overexpressing advanced G/GEA. In 2L, doublet chemotherapy regimens are not uniformly more efficacious than single-agent taxanes or irinotecan, and ramucirumab has demonstrated improved outcomes both as monotherapy and in combination. Conclusion: For advanced G/GEA, review of trial results from 2009–2019 support 1L therapy with platinum and fluoropyrimidine and sequencing with taxanes or irinotecan in combination with biologics as effective 2L options. Escalating to a triplet may add some efficacy at the expense of added toxicity. Implications for Practice: The rapidly changing treatment landscape for advanced gastric cancer includes increasing options for refractory disease. With multiple first-line platinum-based regimens, identification of those with the best benefit-to-risk ratio may provide guidance on treatment sequencing strategies. This article presents findings from the published literature of randomized controlled trials that included a first-line platinum/fluoropyrimidine combination and, for second-line trials, patients with platinum/fluoropyrimidine-refractory disease. This guiding summary could be a tool for clinicians to identify the optimal first-line regimen(s) followed by a strategy for subsequent regimens.

Original languageEnglish
Pages (from-to)e1704-e1729
Issue number10
Publication statusPublished - 2021 Oct

Bibliographical note

Funding Information:
Eli Lilly & Co. provided funding to RTI Health Solutions for the SLR and also provided medical writing and editing support, in accordance with Good Publication Practice (GPP3) guidelines ( Hannah M. Messersmith of Eli Lilly & Co. provided writing support for this manuscript. Eli Lilly & Co. contracted with Syneos Health for editorial support provided by Antonia Baldo.

Publisher Copyright:
© 2021 ELI LILLY AND COMPANY. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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