Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases.

Abstract

INTRODUCTION:

Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery.

METHODS:

We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery.

RESULTS:

Thirty-eight patients were included with a median follow-up of 31.6 months. Two-year local control was 92%. Median time to out-of-field CNS and extra-CNS progression were 8.4 and 7.9 months, respectively. Median progression-free survival (PFS) was 3.4 months and median overall survival (OS) was not reached (NR). Twenty-five patients (66%) received anti-CTLA4 and 13 patients (34%) received anti-PD-1+/-anti-CTLA4. Compared with anti-CTLA4, patients that received anti-PD-1+/-anti-CTLA4 had significant improvements in time to out-of-field CNS progression (p = 0.049), extra-CNS progression (p = 0.015), and PFS (p = 0.043), with median time to out-of-field CNS progression of NR vs. 3.1 months, median time to extra-CNS progression of NR vs. 4.4 months, and median PFS of 20.3 vs. 2.4 months. Six patients (16%) developed grade ≥ 2 CNS toxicities (grade 2: 3, grade 3: 3, grade 4/5: 0).

CONCLUSIONS:

Excellent outcomes were observed in patients that initiated CPIs within 8 weeks of undergoing radiosurgery for newly diagnosed MBM. There appears to be an advantage to anti-PD-1 or combination therapy compared to anti-CTLA4.

• Authors: Tyler P Robin, Robert E Breeze, Derek E Smith, Chad G Rusthoven, Karl D Lewis, Rene Gonzalez, Amanda Brill, Robin Saiki, Kelly Stuhr, Laurie E Gaspar, Sana D Karam, David Raben, Brian D Kavanagh, Sameer K Nath, Arthur K Liu
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 140 Issue 1 Pg. 55-62 (Oct 2018) ISSN: 1573-7373 [Electronic] United States
• PMID: 29909499 (Publication Type: Journal Article)

Chemical References

• Antibodies
• CTLA-4 Antigen
• CTLA4 protein, human
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Aged
• Aged, 80 and over
• Antibodies (therapeutic use)
• Brain Neoplasms (drug therapy, secondary, surgery)
• CTLA-4 Antigen (immunology)
• Combined Modality Therapy
• Disease Progression
• Female
• Humans
• Longitudinal Studies
• Male
• Melanoma (pathology)
• Programmed Cell Death 1 Receptor (immunology)
• Progression-Free Survival
• Radiosurgery (methods)
• Retrospective Studies
• Statistics, Nonparametric
• Treatment Outcome