Stereotactic radiosurgery with and without checkpoint inhibition for patients with metastatic non–small cell lung cancer to the brain: a matched cohort study

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OBJECTIVE

Immune checkpoint inhibitors (ICIs) improve survival in patients with advanced non–small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICIs in patients with NSCLC excluded patients with untreated brain metastases (BMs). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, the authors sought to define the safety and radiological and clinical outcomes for patients with NSCLC-BMs treated with concurrent ICI and SRS.

METHODS

A retrospective matched cohort study was performed on patients who had undergone SRS for one or more NSCLC-derived BMs. Two matched cohorts were identified: one that received ICI before or after SRS within a 3-month period (concurrent ICI) and one that did not (ICI naive). Locoregional tumor control, peritumoral edema, and central nervous system (CNS) adverse events were compared between the two cohorts.

RESULTS

Seventeen patients (45 BMs) and 34 patients (92 BMs) composed the concurrent-ICI and ICI-naive cohorts, respectively. There was no statistically significant difference in overall survival (HR 0.99, 95% CI 0.39–2.52, p = 0.99) or CNS progression-free survival (HR 2.18, 95% CI 0.72–6.62, p = 0.11) between the two groups. Similarly, the 12-month local tumor control rate was 84.9% for tumors in the concurrent-ICI cohort versus 76.3% for tumors in the ICI-naive cohort (p = 0.94). Further analysis did reveal that patients receiving concurrent ICI had increased rates of CNS complete response for BMs treated with SRS (8/16 [50%] vs 5/32 [15.6%], p = 0.012) per the Response Assessment in Neuro-Oncology (RANO) criteria. There was also a shorter median time to BM regression in the concurrent-ICI cohort (2.5 vs 3.1 months, p < 0.0001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in the patients receiving concurrent ICI (5.9% vs 2.9% in ICI-naive cohort, p = 0.99). There was no significant difference in the rate of peritumoral edema progression between the two groups (concurrent ICI: 11.1%, ICI naive: 21.7%, p = 0.162).

CONCLUSIONS

The concurrent use of ICI and SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent ICI did not increase peritumoral edema or rates of radiation necrosis. Further studies are needed to evaluate whether combined ICI and SRS improves progression-free survival and overall survival for patients with metastatic NSCLC.

ABBREVIATIONS ALC = absolute lymphocyte count; BM = brain metastasis; CNS = central nervous system; ICI = immune checkpoint inhibitor; KPS = Karnofsky Performance Status; NSCLC = non–small cell lung cancer; OS = overall survival; PACS = picture archiving and communication system; PD-1 = programmed death receptor 1; PD-L1 = programmed death ligand 1; PEV = peritumoral edema volume; PFS = progression-free survival; RANO = Response Assessment in Neuro-Oncology; RPA = recursive partitioning analysis; SRS = stereotactic radiosurgery.

Article Information

Correspondence Jason P. Sheehan: University of Virginia Health System, Charlottesville, VA. jsheehan@virginia.edu.

INCLUDE WHEN CITING Published online July 26, 2019; DOI: 10.3171/2019.4.JNS19822.

Disclosures Dr. Gentzler is a consultant for AstraZeneca, Merck, Takeda (Ariad), Bristol Myers Squibb, and Clovis Oncology and has received research funding from Merck, Bristol Myers Squibb, Helsinn, and Takeda for the study described.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Kaplan-Meier analysis of patients and their treated BMs following SRS. A: There was no statistically significant difference in PFS between patients receiving concurrent ICI and those who did not (p = 0.11, log-rank test). The 12-month actuarial PFS rate for the concurrent-ICI cohort (dashed line) was 47.6% versus 63.4% for the ICI-naive cohort (solid line). B: The median time to individual BM regression was shorter in patients receiving ICIs (2.5 months) than in those who did not (3.1 months; p < 0.0001, log-rank test). C: BMs with peritumoral edema had a shorter median time to edema regression in patients who received ICI (2.4 vs 3.1 months; p < 0.001, log-rank test).

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