The impact of epidermal growth factor receptor mutations on patterns of disease recurrence after chemoradiotherapy for locally advanced non–small cell lung cancer: a literature review and pooled analysis

Abstract

The purpose of this review was to evaluate the impact of epidermal growth factor receptor (EGFR) mutation status on disease recurrence in patients treated with chemoradiotherapy (CRT) for locally advanced non–small cell lung cancer (NSCLC). A literature search was conducted and a total of three studies were analyzed. There was no significant difference in the objective response rate between the EGFR mutation group and the EGFR wild-type group (odds ratios [OR] 1.46, 95% CI, 0.79–2.70, P = 0.228), and there was no significant difference in the incidence of disease recurrence (OR 1.37, 95% CI, 0.68–2.75, P = 0.379) between the two groups. There were significant difference in the incidence of local/locoregional progression (LP) (OR 0.35, 95% CI, 0.18–0.71, P = 0.003) and distant progression (DP) (OR 2.97, 95% CI, 1.59–5.54, P < 0.001). Brain metastasis (BM) was one of the main recurrence patterns of DP, and the incidence was significantly higher in the EGFR mutant group (OR 2.75, 95% CI, 1.43–5.31, P = 0.003). There were no statistically significant heterogeneities in these pooled analyses. The patterns of recurrence after CRT for locally advanced NSCLC were different according to EGFR mutation status. LP after CRT in patients with EGFR mutation was less frequent, but the high incidence of DP, especially BM, continued to be the major problem. On the other hand, LP continued to be the major problem in EGFR wild-type patients. In multimodality treatment for inoperable locally advanced NSCLC, we may need to consider different treatment strategies according to EGFR mutation status.

Comparative effectiveness of concurrent chemoradiotherapy versus EGFR‐tyrosine kinase inhibitors for the treatment of clinical stage IIIb lung adenocarcinoma patients with mutant EGFR

“…A phase III trial reported five‐year OS rates in stage III NSCLC patients treated with CCRT of 23% to 32% (for 74 Gy and 60 Gy, respectively) . Furthermore, longer survival was reported in a 2017 study of locally advanced NSCLC patients with m EGFR (vs. wild EGFR ) treated with CCRT, although the prognostic significance of m EGFR on recurrence was debated in a review paper published in 2016 . In the TKI group, our five‐year OS result was 26%, close to the 25% estimated in a recent systematic review (see Appendix B).…”

Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: a systematic review and meta-analysis

“…Our results were consistent with published meta-analyses that demonstrated that EGFR sensitizing mutations were not prognostic for localized NSCLC treated with definitive chemoradiotherapy or surgery [ 17 – 19 ]. Ochiai and colleagues performed a systematic review and meta-analysis of three retrospective non-randomized comparative studies to determine the impact of EGFR sensitizing mutations in locally advanced NSCLC treated with concurrent chemo-radiotherapy on patterns of recurrence, recurrence-free and overall survival [ 17 ]. They found that there was no difference in disease recurrence, recurrence free and overall survival between EGFR mutated and EGFR wild-type NSCLC, but there was a higher incidence of distant disease recurrence rate and lower incidence of locoregional recurrence rate for EGFR mutated NSCLC.…”

Real‐world outcomes of chemoradiotherapy for unresectable Stage III non‐small cell lung cancer: The SOLUTION study

“…Other studies have also assessed the impact of EGFR mutations on treatment outcomes. 26,27 Ochiai et al 26 found no differences in the objective response rate (odds ratio 1.46, 95% CI 0.79-2.70) or the disease recurrence rate (odds ratio 1.37, 95% CI 0.68-2.75) after CRT between the EGFRm+ and EGFR wild-type groups. On the other hand, Tanaka et al 27 reported that PFS was significantly shorter in the EGFRm+ group and that the ratio of distant metastasis in patients with disease recurrence was relatively higher in this group than the EGFR wild-type group.…”