Analysis of progression-free survival of first-line tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring leu858Arg or exon 19 deletions

Abstract

BackgroundGefitinib, erlotinib and afatinib provide remarkable response rates and progression-free survival compared to platinum-based chemotherapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor-activating mutations, and are therefore standard first-line treatment in these patients. However, no study has compared these drugs regarding progression-free survival.Materials and MethodsWe conducted this retrospective study at a single medical center in Taiwan from February 16, 2011 to October 30, 2015. We used the Kaplan-Meier method to estimate survival, and multivariate Cox proportional hazard models to estimate adjusted hazard ratios and 95% confidence intervals.FindingsOf the 1006 patients diagnosed with stage IIIb and IV non-small cell lung cancer in the study period, 448 (44.5%) had EGFR-activating mutations and received first-line therapy with gefitinib (n = 304, 67.6%), erlotinib (n = 63, 14.3%), or afatinib (n = 81, 18.1%). The median duration of follow-up for progression-free survival was 12.1 months in the gefitinib arm (Interquartile range [IQR]: 5.5–16.5), 11.2 months in the erlotinib arm (IQR: 4.9–16.7), and 10.3 months in the afatinib arm (IQR: 7.0–14.2). Progression-free survival was significantly longer in the patients who received afatinib or erlotinib compared to those who received gefitinib (log-rank test, p < 0.001), and the median progression-free survival was 11.4 months in the gefitinib group.InterpretationAfatinib and erlotinib provide significant benefits in progression-free survival compared to gefitinib in first-line treatment of patients with non-small-cell lung cancers harboring EGFR-activating mutations. Further clinical trials are warranted to validate these findings.

Comparison of gefitinib, erlotinib and afatinib in non‐small cell lung cancer: A meta‐analysis

“…Compared with erlotinib, afatinib appeared to have similar efficacy in terms of progression‐free survival as first‐line treatment of EGFR mutant patients, but was associated with longer progression‐free survival (2.6 vs . 1.9 months, HR 0.81, 95% CI, 0.69 to 0.96) and overall survival (7.9 vs .…”

“…The effects of afatinib were investigated in four studies, including two observational ones directly comparing the three agents on progression-free survival 89 or selected adverse events, 98 one randomized trial comparing afatinib with gefitinib on all efficacy and safety outcomes, 97 and one randomized trial comparing afatinib with erlotinib on all efficacy and safety outcomes. 103 Compared with gefitinib, afatinib appeared to be associated with longer progression-free survival as first-line treatment of EGFR mutant patients, 89,97 but the benefit was considerably different between studies (>18 versus 11.4 months in the observational one; 11.0 versus 10.9 months in the randomized trial), and there was no evidence that afatinib prolonged overall survival.…”

“…The effects of afatinib were investigated in four studies, including two observational ones directly comparing the three agents on progression-free survival 89 or selected adverse events, 98 one randomized trial comparing afatinib with gefitinib on all efficacy and safety outcomes, 97 and one randomized trial comparing afatinib with erlotinib on all efficacy and safety outcomes. 103 Compared with gefitinib, afatinib appeared to be associated with longer progression-free survival as first-line treatment of EGFR mutant patients, 89,97 but the benefit was considerably different between studies (>18 versus 11.4 months in the observational one; 11.0 versus 10.9 months in the randomized trial), and there was no evidence that afatinib prolonged overall survival. 97 Compared with erlotinib, afatinib appeared to have similar efficacy in terms of progression-free survival as first-line treatment of EGFR mutant patients, 89 but was associated with longer progression-free survival (2.6 vs. 1.9 months, HR 0.81, 95% CI, 0.69 to 0.96) and overall survival (7.9 vs. 6.8 months, HR 0.81, 95% CI, 0.69 to 0.95) as second-line treatment of patients with advanced squamous cell carcinoma of the lung.…”

Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer

“…Meanwhile, a recent study analyzing the BM subgroups of the LUX-Lung 3 and LUX-Lung 6 trials revealed a significant improvement in PFS for the afatinib group compared with the chemotherapy group. 4 Although the effects of afatinib have been compared with those of other EGFR-TKIs, including one observational study that compared three agents in terms of PFS 19 and one randomized trial that compared afatinib with gefitinib, 20 there has been no previous study comparing three TKIs in terms of the prevention and treatment of BM. In our study, the median PFS (8.2 months) of the BM patients who received afatinib was similar to that (8.2 months) reported for the results of the LUX-Lung 3 and LUX-Lung 6 trials, 6 and to that reported for real-world practice (9.2 months).…”

Quality Assessment of Reporting Performance for EGFR Molecular Diagnosis in Non-Small Cell Lung Cancer

“…Many studies have reported that the NSCLC patients with different EGFR gene mutations undergo different responses to first-, second-, and third-generation EGFR-TKIs. These patients also display different progression-free survival (PFS) and OS [19][20][21][22][23]. NSCLC patients harboring deletions in exon 19 respond better to EGFR-TKIs with longer PFS and OS compared with other mutations [19,20].…”