Xu-Yuan Li1, Jia-Zhou Lin2, Shu-Han Yu3. 1. Department of Medical Oncology, Shantou Central Hospital, Shantou, China. Electronic address: lxuyuan@qq.com. 2. Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, China. 3. Department of Medical Oncology, Shantou Central Hospital, Shantou, China.
Abstract
PURPOSE: Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were firmly established as front-line treatment for non-small cell lung cancer (NSCLC) that harbored an activating EGFR mutation. Gefitinib or erlotinib was considered the standard of care. TKI-based combination therapy has been investigated and has shown encouraging results. METHODS: The PubMed and EMBASE databases, the Cochrane Central Register of Controlled Trials, and meeting abstracts were screened for relevant studies between January 2000 and February 2019. Prospective randomized controlled trials were included that investigated EGFR TKIs (alone or in combination) in untreated patients with NSCLC whose tumors had sensitive EGFR mutations. A frequentist random effects network meta-analysis model was conducted to assess objective response rate, progression-free survival, and overall survival. P-score was used to rank treatment effects. FINDINGS: Seventeen trials involving 9 treatments and 4373 patients were included. Heterogeneity existed in the network analysis. For progression-free survival, the top 3 treatments were osimertinib, standard of care plus chemotherapy, and standard of care plus bevacizumab; corresponding p-scores were 0.88, 0.79, and 0.75, respectively. For overall survival, the top 3 treatments were standard of care plus chemotherapy, osimertinib, and dacomitinib; corresponding p-scores were 0.89, 0.85, and 0.64. TKI-based combination therapy caused more toxicity than a TKI alone. IMPLICATIONS: Osimertinib seemed to be a better option as upfront therapy for EGFR-mutant NSCLC in terms of efficacy and tolerability.
PURPOSE: Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were firmly established as front-line treatment for non-small cell lung cancer (NSCLC) that harbored an activating EGFR mutation. Gefitinib or erlotinib was considered the standard of care. TKI-based combination therapy has been investigated and has shown encouraging results. METHODS: The PubMed and EMBASE databases, the Cochrane Central Register of Controlled Trials, and meeting abstracts were screened for relevant studies between January 2000 and February 2019. Prospective randomized controlled trials were included that investigated EGFR TKIs (alone or in combination) in untreated patients with NSCLC whose tumors had sensitive EGFR mutations. A frequentist random effects network meta-analysis model was conducted to assess objective response rate, progression-free survival, and overall survival. P-score was used to rank treatment effects. FINDINGS: Seventeen trials involving 9 treatments and 4373 patients were included. Heterogeneity existed in the network analysis. For progression-free survival, the top 3 treatments were osimertinib, standard of care plus chemotherapy, and standard of care plus bevacizumab; corresponding p-scores were 0.88, 0.79, and 0.75, respectively. For overall survival, the top 3 treatments were standard of care plus chemotherapy, osimertinib, and dacomitinib; corresponding p-scores were 0.89, 0.85, and 0.64. TKI-based combination therapy caused more toxicity than a TKI alone. IMPLICATIONS: Osimertinib seemed to be a better option as upfront therapy for EGFR-mutant NSCLC in terms of efficacy and tolerability.