Double-dose icotinib may induce the emergence of the EGFR exon 20 T790M mutation in non-small cell lung cancer patients harboring EGFR-sensitive mutation

Abstract

BackgroundAcquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) inevitably occurs in non-small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations. There are approximately half of the patients who developed resistance to EGFR-TKIs treatment, the mechanism of which remains undiscovered. We occasionally found that double-dose icotinib as further-line salvage treatment may induce the emerging mutation of EGFR exon 20 T790M in NSCLC patients. The present study, therefore, was conducted to explore the probability of the emerging T790M mutation after exposure to double-dose icotinib in metastatic NSCLC patients.Patients and MethodsMetastatic NSCLC patients who received double-dose icotinib as salvage treatment after progression on first-generation TKIs and systematic chemotherapy were screened. Thereafter, patients who received a repeated next-generation sequencing (NGS) test with tumor sample were further enrolled. The procedure of NGS was performed with the standard criteria. Finally, the clinical characteristics, treatment procedures, and outcomes of eligible patients were reviewed and presented.ResultsThree patients have been detected with the emerging T790M mutation after double-dose icotinib exposure, with a mutation frequency of 19.6%, 8.2%, and 87.5%. During the treatment of targetable TKIs including almonertinib or osimertinib, partial response was observed in two patients, and stable disease was observed in the other. The progression-free survival by targetable TKIs for the patients was 3.7+ months (still in extension), 4.9+ months (still in extension), and 6.3 months. Manageable adverse events were observed during the treatment of TKIs.ConclusionThe results of the present study revealed that the emerging EGFR exon 20 T790M mutation might be induced by double-dose icotinib exposure in further-line treatment. Patients with the emerging T790M mutation responded well to the treatment of targetable TKIs including almonertinib or osimertinib.

Icotinib in a lung adenocarcinoma patient with acquired EGFR 19del/C797S mutation-mediated resistance to osimertinib: a case report

“…Several reports suggest that advanced NSCLC patients with rare EGFR mutations may benefit from icotinib, including P.S.746_S752delinsi [20], double rare EGFR G719D/L861Q mutations, and acquired novel CUX1-MET fusions [21], suggesting that icotinib is a promising EGFR-TKI drug. In one study, a double dose of icotinib in NSCLC patients with EGFRsensitive mutations induced the appearance of T790M in previously T790m-negative patients for subsequent third-generation targeted therapy [22]. A prospective, multiscale study in 2023 evaluating the efficacy of icotinib along with erlotinib in advanced EGFR-mutationpositive NSCLC demonstrated that the regimen was effective and well tolerated regardless of comutation [23].…”