A network meta-analysis of nonsmall-cell lung cancer patients with an activating EGFR mutation

Abstract

Background:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line treatment for nonsmall-cell lung cancer (NSCLC) patients with an activating EGFR mutation. Osimertinib, compared with erlotinib or gefitinib, showed an improvement in progression-free survival (PFS) in a recent trial. The authors compared EGFR TKIs in terms of PFS in a network meta-analysis.Methods:The PubMed and Embase databases and meeting abstracts were screened for relevant studies between January 2009 and November 2017. A random-effect frequentist network meta-analysis model was conducted to assess PFS. P-score was used to rank treatment effects.Results:Eleven trials with 3145 patients and 5 TKIs (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) were included. Heterogeneity and inconsistency existed in the network analysis. Gefitinib and erlotinib had similar effects (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.76–1.15). For all patients, the 3 TKIs with the highest probability of benefit were osimertinib, dacomitinib, and afatinib, with P-scores of 91%, 78%, and 46%, respectively. Compared with erlotinib or gefitinib, osimertinib was associated with improvement in men (HR = 0.79, 95% CI, 0.68–0.92), non-Asians (HR = 0.63, 95% CI, 0.40–0.98), smokers (HR = 0.73, 95% CI, 0.56–0.95), and those with a Del19 mutation (HR = 0.69, 95% CI, 0.54–0.90); dacomitinib and afatinib showed no improvement. Toxicity profiles mostly overlapped in all the EGFR TKIs. Toxicity-related death was rare.Conclusions:Osimertinib was shown to be the best agent to achieve the longest PFS in NSCLC patients with an activating EGFR mutation. However, the benefit of osimertinib might be restricted to certain subgroups.

Efficacy and Safety of Tyrosine Kinase Inhibitors in Advanced Non-Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutation: a Network Meta-Analysis

“…In comparison to other published NMAs, this NMA included more trials and thus had a bigger sample size. Additionally, a NMA published in 2018 only reported PFS as efficacy outcome and did not report any ORR or OS results, while all outcomes were included in this NMA [ 40 ]. Erlotinib and gefitinib were combined in one arm in the previously published NMA, while they were analyzed separately in this NMA [ 40 ].…”

“…Additionally, a NMA published in 2018 only reported PFS as efficacy outcome and did not report any ORR or OS results, while all outcomes were included in this NMA [ 40 ]. Erlotinib and gefitinib were combined in one arm in the previously published NMA, while they were analyzed separately in this NMA [ 40 ]. Further, only the PFS ranking scores were reported in the previously published article [ 40 ].…”

“…Erlotinib and gefitinib were combined in one arm in the previously published NMA, while they were analyzed separately in this NMA [ 40 ]. Further, only the PFS ranking scores were reported in the previously published article [ 40 ]. Notably, we reported ranking order for OS as well.…”

Comparative Efficacy of Targeted Therapies in Patients with Non-Small Cell Lung Cancer: A Network Meta-Analysis of Clinical Trials

“…The RR (95% CI) for ORR and HR (95% CI) for PFS were 1.05 (1.00-1.11) and 1.00 (0.95-1.04), respectively [20]. Another network meta-analysis of 11 clinical trials also showed the similar PFS between gefitinib and erlotinib [21]. However, unlike our findings, the third-generation EGFR inhibitor osimertinib was found to have a longer PFS (HR 0.71, 95% CI 0.54-0.95), and the significant difference between the second-generation EGFR inhibitor afatinib and standard of care (either gefitinib or erlotinib) was not observed (HR 0.96, 95% CI, 0.86-1.17) [21].…”

Receptor Tyrosine Kinase-Targeted Cancer Therapy

“…Moreover, the FLAURA study demonstrated that osimertinib was more effective in improving PFS as a first-line treatment for EGFR mutation-positive advanced NSCLC compared to standard EGFR-TKIs (gefitinib or erlotinib) with a similar safety profile and lower rates of serious adverse events [ 100 ]. A recent network meta-analysis (NMA) revealed that osimertinib was the best therapeutic agent among five major EGFR TKIs as first-line treatments because it achieved the longest PFS of patients with NSCLC containing EGFR -activating mutations [ 101 ]. We performed a NMA using the statistical method of the frequentist approach [ 102 ] to evaluate four phase III trials [ 100 , 103 , 104 , 105 ] including 1305 patients for PFS to examine first-line treatment of NSCLC with EGFR -activating mutations.…”