PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice
- 15 August 2020
- journal article
- review article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 26 (16), 4186-4197
- https://doi.org/10.1158/1078-0432.CCR-20-0798
Abstract
Immune checkpoint inhibitors (ICI) have revolutionized the management of advanced non-small cell lung cancer (NSCLC). However, most pivotal phase III trials systematically excluded patients with active brain metastases, precluding the generalization of the results. Although theoretically restricted from crossing the blood-brain barrier, the novel pharmacokinetic/pharmacodynamic profiles of anti-PD-1/PD-L1 drugs have prompted studies to evaluate their activity in patients with NSCLC with active central nervous system (CNS) involvement. Encouraging results have suggested that ICI could be active in the CNS in selected patients with driver-negative advanced NSCLC with high PD-L1 expression and low CNS disease burden. Single-agent CNS response rates around 30% have been reported. Beyond this particular setting, anti-PD-1/PD-L1 antibodies have been evaluated in patients receiving local therapy for brain metastases (BM), addressing concerns about potential neurologic toxicity risks associated with radiotherapy, more specifically, radionecrosis (RN). Accordingly, a variety of clinical and imaging strategies are being appropriately developed to evaluate tumor response and to rule out pseudoprogression or radionecrosis. Our purpose is to critically summarize the advances regarding the role of systemic anti-PD-1/PD-L1 antibodies for the treatment of NSCLC BM. Data were collected from the PubMed database, reference lists, and abstracts from the latest scientific meetings. Recent reports suggest anti-PD-1/PD-L1 agents are active in a subset of patients with NSCLC with BM showing acceptable toxicity. These advances are expected to change soon the management of these patients but additional research is required to address concerns regarding radionecrosis and the appropriate sequencing of local and systemic therapy combinations.Funding Information
- Stand Up To Cancer American Cancer Society (SU2C-AACR-DT17-15)
- Yale (P50 CA121974)
- Lung Cancer (PA50 CA196530)
This publication has 91 references indexed in Scilit:
- Delayed Radiation-Induced Vasculitic LeukoencephalopathyInternational Journal of Radiation Oncology*Biology*Physics, 2012
- Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinomaNeuro-Oncology, 2012
- Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosisRadiation Oncology, 2011
- Activity of Pemetrexed on brain metastases from Non-Small Cell Lung CancerLung Cancer, 2010
- Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood–brain barrierAnti-Cancer Drugs, 2007
- Distribution of the Novel Antifolate Pemetrexed to the BrainThe Journal of pharmacology and experimental therapeutics, 2005
- Incidence Proportions of Brain Metastases in Patients Diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance SystemJournal of Clinical Oncology, 2004
- Temozolomide for the Treatment of Brain Metastases Associated With Metastatic Melanoma: A Phase II StudyJournal of Clinical Oncology, 2004
- Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediatedInternational Journal of Radiation Oncology*Biology*Physics, 2004
- Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartmentBlood, 2003