The role of targeted therapy and immune therapy in the management of non-small cell lung cancer brain metastases

Abstract

Brain metastases are a significant source of morbidity and mortality in patients with non-small cell lung cancer. Historically, surgery and radiation therapy have been essential to maintaining disease control within the central nervous system due to poorly penetrant conventional chemotherapy. With the advent of targeted therapy against actionable driver mutations, there is potential to control limited and asymptomatic intracranial disease and delay local therapy until progression. In this review paper, intracranial response rates and clinical outcomes to biological and immune therapies are summarized from the literature and appraised to assist clinical decision making and identify areas for further research. Future clinical trials ought to prioritize patient-centered quality of life and neurocognitive measures as major outcomes and specifically stratify patients based on mutational marker status, disease burden, and symptom acuity.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases

“…Several novel and newer-generation TKIs with improved CNS penetrance are currently used in the clinical practice. Erlotinib, gefitinib (1st generation), and afatinib (2nd generation) have intracranial activity in NSCLC patients with EGFR mutations, with objective response rates ranging from 60–80% 25 . However, Osimertinib (3rd generation) was significantly associated with better hazard ratio (HR) for CNS progression-free survival (0.48; 95% CI: 0.26–0.86) compared with gefitinib or erlotinib as the first-line treatment 26 .…”

M2‐like tumor‐associated macrophages promote epithelial–mesenchymal transition through the transforming growth factor β/Smad/zinc finger e‐box binding homeobox pathway with increased metastatic potential and tumor cell proliferation in lung squamous cell carcinoma

“…Lung squamous cell carcinoma (LUSC), an important subtype of non‐small cell lung cancer, accounts for approximately 30% of patients with non‐small cell lung cancer. 1 Despite the development of novel therapies for lung cancer, such as molecular‐targeted therapies and immune checkpoint inhibitors, 2 treating LUSC remains a challenge. Molecular‐targeted therapies, including epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors, are not applied for LUSC because most patients with advanced LUSC do not carry mutations in driver genes.…”