Efficacy of Icotinib, an EGFR Tyrosine Kinase Inhibitor in Non-Small Cell Lung Cancer Patients with Exon 19 Deletion and Exon 21 L858R: A Retrospective Analysis in China

Abstract

<b><i>Introduction:</i></b> The effect of icotinib on non-small cell lung cancer (NSCLC) patients with <i>EGFR</i> exon 19 deletions (19-Del) or L858R point mutation in exon 21 (21-L858R) remains inconsistent. This study aimed to evaluate the efficacy and safety of icotinib in patients with advanced NSCLC harboring these 2 <i>EGFR</i> mutations. <b><i>Methods:</i></b> We retrospectively assessed the clinical effects of first-line icotinib on advanced NSCLC patients with 2 classic <i>EGFR</i> mutations. Kinase activity assays were used to reaffirm the preclinical efficacy. <b><i>Results:</i></b> Among 2,757 patients, 2,365 (86%) harbored 19-Del (1,346/2,757, 49%) or 21-L858R (1,019/2,757, 37%) mutation. Patients with 19-Del had a higher response rate (ORR; 67.8 vs. 62.1%; <i>p</i> = 0.0039) and disease control rate (98.5 vs. 97.2%; <i>p</i> = 0.0223) than those with 21-L858R mutation. The median progression-free survival (PFS) in the 19-Del group (22.3 months, 95% confidence interval [CI]: 21.3–23.4) was significantly longer than that in the 21-L858R group (20.4 months, 95% CI: 19.5–21.7) (<i>p</i> = 0.004). In multivariate analysis, mutation types, clinical stage, and smoking history were significant factors for PFS. Additionally, an in vitro study indicated the 50% inhibitory concentrations (IC<sub>50</sub>) of icotinib was lower for <i>EGFR</i> 19-Del than 21-L858R. <b><i>Conclusion:</i></b> These results suggest that <i>EGFR</i> 19-Del confers superior PFS and response to the icotinib treatment compared to 21-L858R.

Comparative efficacy and safety of almonertinib and osimertinib for advanced non-cellular lung cancer: a real-world non-inferiority study

“…In our study, female patients, those with a history of surgery, a history of radiotherapy, an EGFR-19del mutation, or an ECOG performance status score of 0-1 had an observed progression-free survival bene t, which occurred both in patients administered with almonertinib and in those receiving osimertinib. We also noticed a greater bene t of EGFR-TKI in the EGFR-19del compared to the EGFR-L858R mutant population, which also suggests the greater propensity of the EGFR-L858R mutant population to EGFR-TKI resistance [5,20]. In a subgroup analysis, we reported shorter PFS with almonertinib compared to osimertinib in patients without the EGFR-T790M mutation but not in patients with the EGFR-T790M mutation.…”

EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-Mutated NSCLC: A Prospective, Randomized, Exploratory Study

“…In this cohort, nearly 52% (48/92) of patients carried the EGFR L858R mutation. A previous study has shown that patients harbored EGFR 19_Del confers lower PFS with icotinib than those harbored EGFR L858R mutations [ 26 ]. Therefore, the distribution of EGFR L858R and EGFR 19_Del may be the cause of a shorter PFS than previous studies.…”