Comparing overall survival between first generation EGFR-TKIs and chemotherapy in lung cancer patients with Del19/L858R

Abstract

ObjectiveCombined overall survival (OS) analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor (EGFR) exon 19 deletions (Del19) would benefit from first-line second generation EGFR tyrosine kinase inhibitors (TKIs) afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups.MethodsEligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios (HRs). All measures were pooled using randomeffects models and 95% confidential interval (95% CI) was calculated.ResultsA total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials (RCTs), first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy (pooled HRTKI/Chemo for Del19: 0.82, 95% CI: 0.64-1.06, P = 0.14; pooled HRTKI/Chemo for L858R: 1.15, 95% CI: 0.85-1.56, P = 0.38). Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference (pooled HR19/21: 0.88, 95% CI: 0.67-1.16, P = 0.37).ConclusionsAmong patients with advanced non-small cell lung cancer (NSCLC) harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.

Combined plasma and tissue genotyping of EGFR T790M benefits NSCLC patients: a real‐world clinical example

“…Many groups have explored whether initial EGFRactivating mutation subtypes might serve as a prognostic factor for TKI treatment and possible TKI resistance with T790M mutation (Deng et al, 2016;Ma et al, 2017;Matsuo et al, 2016;O'Kane et al, 2018;Zhuo et al, 2017). Recently, a meta-analysis by Wu (Deng et al, 2016).…”

“…In the recent two decades, treatment of non-small-cell lung cancer (NSCLC), which accounts for 85% of lung cancer patients, has evolved to a great extent (Lamb and Scott, 2017;Lin et al, 2014;Siegel et al, 2018;Wu and Shih, 2018) . Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide favorable treatment options for patients who carry EGFR-activating mutations, which most commonly appear in exon 19 (19del) and in exon 21 (L858R) (Deng et al, 2016;Ettinger et al, 2013). However, patients with advanced NSCLC harboring EGFR-activating mutations develop progressive disease (PD) in a median response period of 10-12 months after taking first-generation TKIs, such as erlotinib and gefitinib (Lin et al, 2014;O'Kane et al, 2018;Tan et al, 2018;Wu and Shih, 2018).…”

Survival difference between EGFR Del19 and L858R mutant advanced non-small cell lung cancer patients receiving gefitinib: a propensity score matching analysis

“…Many retrospective and prospective studies, as well as meta-analyses, that have studied NSCLC patients with various lines of EGFR-TKI treatment have demonstrated longer progression-free survival (PFS) and occasionally more favorable overall survival (OS) in those with Del19 than in those with the L858R or other mutations (6)(7)(8). In contrast, other clinical studies, including phase III trials, have demonstrated no difference in the efficacy of EGFR-TKI treatment according to the EGFR mutation type (9)(10)(11)(12). Therefore, whether there are differences in survival between patients with these common EGFR mutations remains controversial.…”

Clinical Characteristics and Survival Outcomes for Non-Small-Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Double Mutations

“…EGFR-TKI treatment was more effective than chemotherapy for patients with 19Del mutation. However, for patients with L858R mutation, EGFR-TKI treatment and chemotherapy have similar effect and chemotherapy might even be better [ 49 – 51 ]. Interestingly, in our study, a short PFS was always appreciable if patients were carrying L858R mutation in combination with other mutation.…”