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

Abstract

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.

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

“…Globally, gastroesophageal adenocarcinomas are among the most common causes of cancer related deaths [1]. Treatment still largely relies on conventional cytotoxic agents which are only limitedly effective in the majority of patients [2,3]. According to a comprehensive molecular analysis by The Cancer Genome Atlas (TCGA) Network, gastric cancer (including gastroesophageal junction cancer) can be classified into four subgroups based on its molecular characteristics: Epstein-Barr virus (EBV)-infected tumors, microsatellite instable (MSI) tumors, genomically stable (GS) tumors and chromosomally instable (CIN) tumors [4].…”

<p>Current Molecular Targeted Agents for Advanced Gastric Cancer</p>

“…For instance, vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors have been introduced into clinical practice. 11,12 Some newly developed targeted therapies and their molecular targets are summarized in Figure 1.…”

Survival benefit of anti-angiogenic agents in patients with previously treated advanced gastric or gastroesophageal junction cancer: a meta-analysis

“…Patients treated with apatinib showed significantly longer PFS and OS than those who received placebo. In terms of adverse events, apatinib was associated with the increased incidence of grade 3–4 hand-foot syndrome (9% vs. 1%) and hypertension (6% vs. 0%) [ 17 ]. Regorafenib had been also tested in a randomized, placebo-controlled phase II study of patients with refractory advanced GC or GEJC [ 15 ].…”