Central Nervous System

SS 40 - CNS 3 - CNS Metastasis

289 - Treatment of Brain Metastases With Stereotactic Radiosurgery and Immune Checkpoint Inhibitors: An International Meta-Analysis of Individual Patient Data

Wednesday, October 24
1:30 PM - 1:40 PM
Location: Room 004

Treatment of Brain Metastases With Stereotactic Radiosurgery and Immune Checkpoint Inhibitors: An International Meta-Analysis of Individual Patient Data
E. J. Lehrer1, J. L. Peterson2,3, P. D. Brown4, J. P. Sheehan5, A. Quinones-Hinojosa3, N. G. Zaorsky6, and D. M. Trifiletti2,3; 1Eastern Virginia Medical School, Norfolk, VA, 2Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, 3Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, 4Dept. of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Neurosurgery, University of Virginia, Charlottesville, VA, 6Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA

Purpose/Objective(s): Multiple studies have reported on the safety and efficacy of stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) for the treatment of brain metastases (BMs). However, these studies have inherent limitations of internal validity. Therefore, we performed a meta-analysis of pooled data evaluating SRS and ICI for BMs.

Materials/Methods: A PICOS/PRISMA/MOOSE selection protocol was used to identify 17 studies across 15 institutions in 3 countries that were published between 2013-2018. Inclusion criteria were patients: (1) diagnosed with BMs; (2) treated with SRS and ICI, either concurrently or non-concurrently; (3) with at least one of the primary or secondary outcomes measures reported. Data regarding primary and secondary outcomes, as well as study characteristics, sample size, SRS dose, ICI regimen, follow-up, and median overall survival were recorded for each study. Weighted random effects meta-analyses using the Dersimonian and Laird method was performed for each outcome. Kaplan-Meier curves were digitized to extract individual patient data and were pooled to generate master curves to compare timing of SRS and ICI to overall survival (OS) at 1-year using the log-rank test. The primary outcome was 1-year OS. Secondary outcomes were 1-year local control (LC), 1-year regional brain control, and incidence of radionecrosis. These endpoints were also assessed based on the temporal relationship of SRS and ICI administration

Results: There were 534 patients included across 17 series with 1,570 BMs, the primary tumor studied was melanoma in 16 of the studies, non-small cell lung cancer in 2, and renal cell carcinoma in 1. The median follow-up time was 9.1 months, median patient age was 61.7 years, and median OS from radiosurgery was 12.0 months. The most commonly used ICI were anti cytotoxic T-lymphocyte-associated protein 4 agents, used in 14 of the studies. Anti programmed cell death protein 1 agents were used in 9 of the studies. The most commonly used SRS dose was 20 Gy (range: 18-24 Gy). 1-year OS was 58% (95% confidence interval [CI]: 51.9-63.8%); there was an improvement in OS with concurrent versus non-concurrent ICI and SRS (p<0.01). Regional brain control at 1-year was 33.2%, and it was 38.1% versus 12.3% for concurrent versus non-concurrent therapy (p<0.05). 1-year LC was 89.2% in the concurrent group compared to 67.8% in the non-concurrent group (p=0.09). The incidence of radionecrosis at 1-year was 5.3% (95% CI: 0.3-15.7%). All studies reporting any incidence of radionecrosis involved the use of ipilimumab.

Conclusion: Combination SRS and ICI for BMs is efficacious and safe: 1-year OS is 58% and symptomatic radionecrosis occurs in <10%. Concurrent SRS and ICI is associated with improved OS versus non-concurrent SRS and ICI in selected patients.

Author Disclosure: E.J. Lehrer: None. J.L. Peterson: None. P.D. Brown: Honoraria; UptoDate. J.P. Sheehan: secretary; N2QOD. A. Quinones-Hinojosa: None. N.G. Zaorsky: None. D.M. Trifiletti: Research Grant; Novocure. Member; ARRO.

Eric Lehrer, MD, MS

Disclosure:
No relationships to disclose.

Presentation(s):

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