Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

Abstract

Background: Osimertinib—the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)—has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs.Methods: Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n=183), afatinib (n=55), or osimertinib (n=150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR).Results: In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs.Conclusion: Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.

Successful treatment of lung adenocarcinoma complicated with a rare compound EGFR mutation L833V/H835L using aumolertinib: a case report and literature review

“…Despite experiencing disease progression after six previous lines of therapy, including a 1month course of gefitinib, chemotherapy, and afatinib, the patient demonstrated a positive response to osimertinib as the seventh-line therapy, with a duration of more than 3 months (Qin et al, 2018). The use of third-generation TKIs has shown superior efficacy in the treatment of central nervous system metastases (CNS) compared to platinum chemotherapy and first/secondgeneration EGFR-TKIs (Gen et al, 2022). This is attributed to their ability to cross the blood-brain barrier and effectively penetrate the CNS.…”

EGFR is a potential dual molecular target for cancer and Alzheimer’s disease

“…Osimertinib targets EGFR T790, which is resistant to most firstand second-generation EGFR TKIs (Janjigian et al, 2014;Jiang and Zhou, 2014;Barbuti et al, 2019). Osimertinib is known for its clinical activities in glioblastoma and NSCLC (Makhlin et al, 2019;Gen et al, 2022). In vitro, osimertinib has higher affinity for EGFR L858R/T790M than for wild-type EGFR (Kuijper et al, 2015;Greig, 2016).…”