The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis

Abstract

The prognostic value of epidermal growth factor receptor (EGF-R) for survival of patients with lung cancer remains controversial. The authors performed a systematic review of the literature in order to clarify its impact. Published studies were identified using an electronic search in order to aggregate the available survival results, after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to have dealt with EGF-R assessment in lung cancer patients on the primary site and to have analysed survival according to EGF-R expression. Among the 16 eligible studies, 14 assessed any nonsmall-cell lung cancer (NSCLC) subtype, one adenocarcinoma only and one squamous-cell carcinoma only. The overall median quality score was 56.3%, with no significant difference either between studies assessable or not assessable for meta-analysis or between studies with significant and nonsignificant results. One individual trial reported a survival benefit for patients with EGF-R expression, three a survival disadvantage and 12 no statistically significant difference. Eleven studies (2,185 patients) provided sufficient data to allow a meta-analysis of the survival results. EGF-R expression positivity was determined according to the cut-off as determined by the authors. The meta-analysis showed that EGF-R expression was not a statistically significant prognostic factor for survival in NSCLC. In the subgroup of studies using immunohistochemistry, statistical tests reached a significant level against EGF-R. Epidermal growth factor receptor might be a poor prognostic factor for survival in nonsmall-cell lung cancer. The amplitude of the impact is small, however, and may be subject to publication bias.

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

“…To perform the meta-analysis, we used the same methodology than in our previous systematic reviews (Meert et al, 1999(Meert et al, , 2002aMascaux et al, 2000;Sculier et al, 2001;Steels et al, 2001;Martin et al, 2003). The absence of statistically significant difference in quality scores between significant and nonsignificant publications allowed us to perform a quantitative aggregation of the individual studies results.…”

“…By using the methodology of systematic reviews of the literature with meta-analyses, our Group has shown a prognostic role for several biological factors in lung cancer: p53 , Bcl-2 , vascular endothelial growth factor (VEGF) (Delmotte et al, 2002), epidermal growth factor receptor (EGFR) (Meert et al, 2002a), Neu and microvessel density (Meert et al, 2002b).…”

Predictive value of EGFR and HER2 overexpression in advanced non-small-cell lung cancer

“…Interestingly, although there was no difference in OS between erlotinib-and placebo-treated IHC-negative patients in the BR.21 study, IHC-negative patients in the ISEL study showed a tendency toward a shorter OS with gefitinib (HR, 1.57 (95% CI, 0.86-2.87)) (Tsao et al, 2005;Hirsch et al, 2006). Many studies have also shown that EGFR protein expression is associated with poor prognosis (Meert et al, 2002).…”

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

“…The participation of many readers was a guarantee for the correct interpretation of the articles. The methodological evaluation was scored according to the European Lung Cancer Working Party (ELCWP) scale previously published (Steels et al, 2001) and applied in other meta-analyses (Delmotte et al, 2002;Meert et al, 2002aMeert et al, , b, 2003Martin et al, 2003Martin et al, , 2004Mascaux et al, 2005a). Each item was assessed using an ordinal scale (possible values: 2, 1, 0).…”

“…In order to clarify the prognostic impact of other biological factors in lung cancer, our group has performed systematic reviews of the literature with meta-analyses. It allowed us to show that VEGF (Delmotte et al, 2002), microvessel density (Meert et al, 2002b), EGFR (Meert et al, 2002a), HER-2/Neu , Ki-67 (Martin et al, 2004), K-Ras (Mascaux et al, 2005a) and p53 (Steels et al, 2001) have a negative impact on survival, whereas Bcl-2 is associated with a favourable survival effect, at least when studying their impact in univariate analysis.…”