Systemic therapy in patients with NSCLC with brain metastasis: the emerging role of immunotherapy

Abstract

Brain metastasis (BM) is very common in advanced non-small cell lung cancer (NSCLC) patients. The development of BM remains a serious complication associated with significant morbidity and mortality. The traditional approach has been largely focusing on local therapy with surgery and/or radiation. New approaches to treat BM in NSCLC are urgently needed to offer safe and effective therapy as well as to preserve neurocognitive function. There has been significant progress in development of systemic therapies to treat advanced NSCLC in recent years. Targeted therapy has been gradually incorporated into clinical practice to manage NSCLC with BM. Immunotherapy (IO) has revolutionized our treatment paradigm to manage advanced NSCLC. In this review we outline the systemic options for NSCLC-related BM and discuss IO in NSCLC. Finally, we describe the available data and future perspective to support the use of IO in NSCLC patients with BM.

Combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer

“…In addition to the original studies on combination of radiotherapy and immunotherapy in patients with brain metastases from NSCLC a valuable insight one may find in recent review papers that focus on this subject (2,3,39). Some additional information one may also find in metaanalysis of individual patient data that focused on SRT plus ICI treatment of brain metastases from various primary sites (40), with NSCLC representing only minority of the included studies.…”

Modern era systemic therapies: Expanding concepts of cure in early and locally advanced non‐small cell lung cancer

“…117 Although earlygeneration tyrosine kinase inhibitors (TKIs) had poor brain penetration and/or limited activity against brain metastases, second-and third-generation TKIs such as osimertinib, alectinib and lorlatinib have shown better pharmacokinetic profiles and improved CNS activity and outcomes in tumors with EGFR mutations or ALK translocations. [117][118][119][120][121][122] Single-agent or combination ICI therapy have also shown improvements relative to chemotherapy alone in NSCLC patients with brain metastases. [123][124][125][126][127][128][129][130][131] Long-term outcomes of pivotal trials in the advanced setting can inform issues of survivorship of metastatic patients treated with new immune and targeted therapies.…”

“…Patients with solitary brain metastasis are an important subset of oligometastatic NSCLC since the brain is a common metastatic site 114–117 and blood–brain‐barrier can prevent access of systemic drugs to the central nervous system (CNS) 117 . Although early‐generation tyrosine kinase inhibitors (TKIs) had poor brain penetration and/or limited activity against brain metastases, second‐ and third‐generation TKIs such as osimertinib, alectinib and lorlatinib have shown better pharmacokinetic profiles and improved CNS activity and outcomes in tumors with EGFR mutations or ALK translocations 117–122 . Single‐agent or combination ICI therapy have also shown improvements relative to chemotherapy alone in NSCLC patients with brain metastases 123–131 …”

Real-world impact of brain metastases on healthcare utilization and costs in patients with non-small cell lung cancer treated with EGFR-TKIs in the US

“…The advent of newer, targeted therapies such as immune checkpoint inhibitors, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and anaplastic lymphoma kinase (ALK) inhibitors, has led to a paradigm shift in the treatment of patients with NSCLC [3]. While the management of NSCLC has improved, brain metastases (BM) represent one of the most frequent and lethal complications among these patients [4].…”