Immunotherapy in NSCLC Patients with Brain Metastases

Abstract

Approximately 40% of unselected non-small cell lung cancer (NSCLC) patients develop brain metastases (BMs) during their disease, with considerable morbidity and mortality. The management of BMs in patients with NSCLC is a clinical challenge and requires a multidisciplinary approach to gain effective intracranial disease control. Over the last decade, immune checkpoint inhibitors (ICIs) have emerged as a game-changer in the treatment landscape of advanced NSCLC, with significant improvements in survival outcomes, although patients with BMs are mostly underrepresented in randomized clinical trials. Moreover, the safety and activity of ICIs and radiotherapy combinations compared with single-agent or sequential modalities is still under evaluation to establish the optimal management of these patients. The aim of this review is to summarize the state-of-the-art of clinical evidence of ICIs intracranial activity and the main challenges of incorporating these agents in the treatment armamentarium of NSCLC patients with BMs.

Intracranial and Extracranial Progression and Their Correlation With Overall Survival After Stereotactic Radiosurgery in a Multi-institutional Cohort With Brain Metastases

“…As a surrogate outcome for OS, PFS is now the most common end point used in clinical trials for patients with metastatic malignant neoplasms . Meanwhile, intracranial PFS is increasingly used as a primary end point among oncologic trials of systemic agents with favorable intracranial response rates . In this study, PFS had a high correlation with OS across all primary tumor subgroups.…”

“… 15 Meanwhile, intracranial PFS is increasingly used as a primary end point among oncologic trials of systemic agents with favorable intracranial response rates. 29 , 30 In this study, PFS had a high correlation with OS across all primary tumor subgroups. Both intracranial and extracranial PFS demonstrated higher OS correlation than PFS; however, whether intracranial or extracranial PFS had the highest correlation with OS appeared to differ across primary tumor origin.…”

Inhibition of proliferation and migration of hepatocellular carcinoma by knockdown of KIF3A via NF-κB signal pathway

“…A subsequent study discovered that silencing KIF3A inhibited HepG2 LC cell proliferation. Stroma cells in the tumor microenvironment (TME), particularly immune cells, exert a vital function in modulating cancer cell malignant behavior [27][28][29]. They have been argued to be signi cant for predicting prognosis and treating cancer cases [30,31].…”

Safety and efficacy of immune checkpoint blockade in patients with advanced nonsmall cell lung cancer and brain metastasis

“…The major neurologic complication was brain radionecrosis, which occurred in 9.7% of the population and was significantly associated with tumour volume. 94,95 The management of radiation necrosis in ICI-treated patients constitutes another challenging issue because of the high doses of steroids that are required in this case. Bevacizumab administration and surgery may lessen the impact of steroids on both the IC and EC efficacy of ICI in carefully selected patients.…”

“…Particularly, this combination led to 6.8% grade ≥ 3 toxicity including IC hypertension in 5.1%. The major neurologic complication was brain radionecrosis, which occurred in 9.7% of the population and was significantly associated with tumour volume 94,95 . The management of radiation necrosis in ICI‐treated patients constitutes another challenging issue because of the high doses of steroids that are required in this case.…”