PD-1/PD-L1 blockers in NSCLC brain metastases: challenging paradigms and clinical practice
Eguren-Santamaria I (1), Sanmamed MF (2), Goldberg SB (3), Kluger HM (4), Idoate MA (5), Lu BY (3), Corral J (1), Schalper KA (6), Herbst RS (3), Gil-Bazo I (7).
Immune checkpoint inhibitors (ICI) have revolutionized the management of advanced non-small cell lung cancer (NSCLC). However, most pivotal phase 3 trials systematically excluded patients with active brain metastases (BM), precluding the generalization of the results.
Though 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 NSCLC patients 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 BM, addressing concerns about potential neurological 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 RN.
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 NSCLC patients 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 RN and the appropriate sequencing of local and systemic therapy combinations.