EGFR tyrosine kinase inhibitors alone or in combination with chemotherapy for non-small-cell lung cancer with EGFR mutations: A meta-analysis of randomized controlled trials.

OBJECTIVE: The objective of this study was to perform a meta-analysis comparing the efficiency of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with chemotherapy to EGFR TKI treatment alone in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Following keyword queries in databases and identification of randomized control trials for inclusion, hazard ratios (HRs), relative risks (RRs), and associated 95% confidence intervals (95% CIs) were determined. RESULTS: Ten randomized controlled trials involving 1354 participants with NSCLC were evaluated. We found that a combined approach of chemotherapy with EGFR TKIs significantly improved overall survival (OS) compared with EGFR TKI alone in our patient cohort (HR = 0.47, 95% CI = 0.31-0.72). In addition, a higher overall response rate (ORR) was found for patients who received combined treatment compared to chemotherapy alone (RR = 2.17, 95% CI = 1.51-3.12). Furthermore, concomitant use of chemotherapy with TKIs significantly improved the progression-free survival (PFS) when compared to the use of TKIs alone (HR = 0.68, 95% CI = 0.49-0.95). Moreover, there was a higher ORR among patients who received combined treatment as compared to those who were managed using TKIs only (RR=1.17, 95%CI=1.09-1.25). CONCLUSION: Our meta-analysis shows that EGFR TKIs with chemotherapy confer better OS and ORR compared to either treatment alone, similarly, the combined treatment showed better PFS and ORR profiles than the use of TKI alone.

Prognostic value of ribonucleotide reductase subunit M1 (RRM1) in non-small cell lung cancer: A meta-analysis.

BACKGROUND: Ribonucleotide reductase subunit 1 (RRM1) is a potential prognostic factor for non-small cell lung cancer (NSCLC). This study evaluates prognostic value of RRM1 in NSCLC patients by meta-analyzing outcomes reported in literature. METHOD: Data were acquired from research articles retrieved after literature search in online databases. Random effects meta-analyses were conducted by pooling hazard ratios (HR). Meta-analyses of standardized mean differences (SMD) were used to evaluate overall survival (OS) and progression-free survival (PFS) between low and high RRM1 expression groups. Metaregression analyses were conducted to evaluate the factors that could affect prognostic relationship of RRM1 with treatment and survival outcomes. RESULTS: 23 studies (3148 patients) were included. RRM1 expression was not meaningfully associated with prognosis of NSCLC even when the reference (HR = 1) was either low RRM1 expression (0.918 [95% CI 0.833, 1.003]) or high RRM1 expression (0.834 [0.625, 1.043]). OS was significantly longer in low RRM1 expression group compared to high RRM1 expression group (SMD 0.73 [0.36, 1.09]; P < 0.0001). PFS was not significantly different between low and high RRM1 expression groups (SMD 0.08 [-0.29, 0.45]; p = 0.68). Age was inversely associated with HR (p = 0.001) even when reference was low RRMI (p = 0.027) or high RRM1 (p = 0.006). Age was positively associated with OS in both low and high RRM1 groups. CONCLUSION: In meta-analysis of studies which used gemcitabine-based therapies, higher RRM1 expression is found to associated with shorter OS but not PFS. HR depicting relationship between RRM1 expression and OS/PFS/treatment response could not demonstrate a prognostic role of RRM1 in NSCLC patients.