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

• Published in: Cancer and metastasis reviews Vol. 35; no. 3; pp. 439 - 456
• Main Authors: ter Veer, Emil, Haj Mohammad, Nadia, van Valkenhoef, Gert, Ngai, Lok Lam, Mali, Rosa M. A., van Oijen, Martijn G. H., van Laarhoven, Hanneke W. M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2016; Springer; Springer Nature B.V
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer patients; Cancer Research; Care and treatment; Chemotherapy; Clinical; Combined Modality Therapy; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Humans; Medical research; Medicine, Experimental; Molecular Targeted Therapy; Neoplasm Staging; Oncology; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retreatment; Stomach Neoplasms - drug therapy; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Treatment Outcome; Chemotherapy; Second-line; Third-line; Targeted therapy; Advanced esophagogastric cancer; Meta-analysis
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-016-9632-2

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.