Does the use of targeted agents in advanced gastroesophageal cancer increase complete response? A meta-analysis of 18 randomized controlled trials

Yanyang Pang,1 Zhen Shen,2 Jiancheng Sun,3 Wu Wang4 1Department of Traditional Chinese Medicine, Hainan Medical University, Haikou, Hainan 571101, China; 2Division of Liver Disease, Huangshi City Hospital of Traditional Chinese Medicine (Infectious Disease Hospital), Edong Healthcare Group, Huangshi, Hubei 435000, China; 3Department of General Surgery, The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; 4Laboratory of Tropical Biomedicine and Biotechnology, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan 571101, China Purpose: We aimed to investigate whether the use of targeted agents (TAs) in advanced gastroesophageal cancer (GEC) increased the complete response (CR) and to assess the surrogate endpoints for survival in the targeted treatment of GEC by using a meta-analysis of randomized controlled trials (RCTs).Methods: Eligible studies were identified using Medline, PubMed, and meeting abstracts. Searches were last updated on April 30, 2018. We calculated the incidence and Peto odds ratio (Peto OR) of CR events in patients assigned to TAs compared with controls. Simple linear regression models were fitted for median overall survival (OS) and each surrogate [median progression-free survival (PFS), CRs, objective response rate (ORR), and disease control rate (DCR), respectively].Results: A total of 7,892 GEC patients from 18 RCTs were included for analysis. The incidence of CR in GEC patients treated with TAs was 2.0% (95% CI, 1.3%–3.0%) compared with 1.7% (95% CI, 1.0%–2.7%) in the control arms. The use of TAs in advanced GEC had a tendency to improve the possibility of archiving CR (Peto OR 1.42; 95% CI, 0.98–2.04; P=0.064) compared with controls. Subgroup analysis according to treatment TAs showed that the addition of antiepidermal growth factor receptor (EGFR) agents to chemotherapy in GEC significantly improved the CR rate in comparison with control (Peto OR 1.77; 95% CI, 1.02–3.09; P=0.044), but not for other molecular TAs (P=0.49 for angiogenesis inhibitors, P=0.66 for mesenchymal-epithelial transition inhibitors). We also found that the addition of TAs to first-line therapy (Peto OR 1.41; 95% CI, 0.94–2.11; P=0.098) had a tendency to increase the chance of obtaining a CR, but not for second-line therapy (Peto OR 1.47; 95% CI, 0.60–3.55; P=0.40). In addition, correlation analysis indicates that PFS, ORR, and DCR were strongly correlated with OS for GEC patients receiving TAs (r=0.85 for PFS; r=0.86 for ORR; r=0.81 for DCR). No marked correlation was found between OS and CRs (r=0.43; P=0.18).Conclusion: Although the CR is a rate event in advanced GEC patients, adding the TAs to therapies, especially for anti-EGFR agents, increases the chance of archiving CR in comparison with the controls. PFS, ORR, and DCR are significantly correlated with OS and could be used as surrogate endpoints in patients with GEC who have received TA therapy, but not for CR. Keywords: gastroesophageal carcinoma, systematic review, novel molecular agent