Second-line treatment of metastatic gastric cancer: Current options and future directions

Abstract

Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase III trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.

Ramucirumab for the treatment of patients with gastric or gastroesophageal junction cancer in community oncology practices

“…Chemotherapy and targeted treatments are recommended for patients with advanced or metastatic gastric or GEJ cancer [4]. Systemic, multi-agent chemotherapy is associated with improved survival in the first-line setting [5]. Preferred second-line treatment options recommended by the National Comprehensive Care Network (NCCN) include cytotoxic agents (i.e., docetaxel, paclitaxel, irinotecan, fluorouracil/ irinotecan), as well as the anti-angiogenic, ramucirumab (used alone or in combination with paclitaxel) [4].…”

Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells

“…Although patients receiving first line therapy may initially respond to treatment, many of them relapse and require a second line of therapy where options are often limited (31). Chemotherapeutic resistance can be attributed to an inherent intrinsic ability of cancer cells to resist the effect of anti-cancer drugs or the development of acquired resistance through mechanisms that include alternations in the target pathways and activation of pro-survival molecules (32).…”

“…Although patients receiving first line therapy may initially respond to treatment, many of them develop recurrence within weeks or months after initial response requiring a second line treatment for disease progression where limited options are available (31). Currently, the only approved targeted therapies for advanced or metastatic gastroesophageal adenocarcinomas are trastuzumab and ramucirumab (34), which reflect the need to test other available targeted therapies.…”

Biomarker analyses of second-line ramucirumab in patients with advanced gastric cancer from RAINBOW, a global, randomized, double-blind, phase 3 study

“…Worldwide cancer statistics record gastric/gastroesophageal junction (GEJ) cancer as a major cause of cancerrelated deaths. About 1 million new cases of gastric cancer occurred in 2012, along with hundreds of thousands of new GEJ cancers, two-thirds with locally advanced or metastatic disease [1,2].…”