Concurrent Radiosurgery and Immune Checkpoint Inhibition

Improving Regional Intracranial Control for Patients with Metastatic Melanoma

Blair Murphy, Joshua Walker, Solange Bassale, Debra Monaco, Jerry Jaboin, Jeremy Ciporen, Matthew Taylor, Charlotte Dai Kubicky

Research output: Contribution to journalArticle

Abstract

Objectives: The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control. Methods: We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined. Results: In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed. Conclusions: Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.

Original languageEnglish (US)
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
DOIs
StateAccepted/In press - Jan 1 2018

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Radiosurgery
Melanoma
Immunotherapy
Disease-Free Survival
Survival
Brain
Neoplasm Metastasis
Therapeutics
Cell Death

Keywords

  • brain metastasis
  • immunotherapy
  • melanoma
  • radiosurgery

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{fce30b3e248e4bfaa7ccd370e46cbe77,
title = "Concurrent Radiosurgery and Immune Checkpoint Inhibition: Improving Regional Intracranial Control for Patients with Metastatic Melanoma",
abstract = "Objectives: The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control. Methods: We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined. Results: In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed. Conclusions: Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.",
keywords = "brain metastasis, immunotherapy, melanoma, radiosurgery",
author = "Blair Murphy and Joshua Walker and Solange Bassale and Debra Monaco and Jerry Jaboin and Jeremy Ciporen and Matthew Taylor and {Dai Kubicky}, Charlotte",
year = "2018",
month = "1",
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T1 - Concurrent Radiosurgery and Immune Checkpoint Inhibition

T2 - Improving Regional Intracranial Control for Patients with Metastatic Melanoma

AU - Murphy, Blair

AU - Walker, Joshua

AU - Bassale, Solange

AU - Monaco, Debra

AU - Jaboin, Jerry

AU - Ciporen, Jeremy

AU - Taylor, Matthew

AU - Dai Kubicky, Charlotte

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control. Methods: We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined. Results: In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed. Conclusions: Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.

AB - Objectives: The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control. Methods: We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined. Results: In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed. Conclusions: Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.

KW - brain metastasis

KW - immunotherapy

KW - melanoma

KW - radiosurgery

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SN - 0277-3732

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