Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases

Abstract

The aim of this study was to evaluate the impact of BRAF inhibitors on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases. We prospectively collected treatment parameters and outcomes for 80 patients with melanoma brain metastases who underwent SRS. Thirty-five patients harbored the BRAF mutation (BRAF-M) and 45 patients did not (BRAF-WT). Univariate and multivariate analyses were performed to identify predictors of overall survival. The median overall survival from first SRS procedure was 6.7, 11.2 months if treated with a BRAF inhibitor and 4.5 months for BRAF-WT. Actuarial survival rates for BRAF-M patients on an inhibitor were 54 % at 6 months and 41 % at 12 months from the time of SRS. In contrast, BRAF-WT had overall survival rates of 28 % at 6 months and 19 % at 12 months. Overall survival was extended for patients on a BRAF inhibitor at or after the first SRS. The median time to intracranial progression was 3.9 months on a BRAF inhibitor and 1.7 months without. The local control rate for all treated tumors was 92.5 %, with no difference based on BRAF status. Patients with higher KPS, fewer treated intracranial metastases, controlled systemic disease, RPA Class 1 and BRAF-M patients had extended overall survival. Overall, patients with BRAF-M treated with both SRS and BRAF inhibitors, at or after SRS, have increased overall survival from the time of SRS. As patients live longer as a result of more effective systemic and local therapies, close surveillance and early management of intracranial disease with SRS will become increasingly important.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501)

“…Our findings indicate that these immune checkpoint inhibitors are effective for controlling not only the primary melanoma but also distant metastases to the brain. Several previous reports have shown a regional immunomodulatory effect and penetration of novel systemic agents into the brain [8,11,12,15,18,20,21,23]. The present results might indicate passage of these agents thorough the bloodbrain barrier in melanoma patients, thereby leading to suppression of new metastases to the brain.…”

BRAF‐V600 mutational status affects recurrence patterns of melanoma brain metastasis

“…42 Further work is needed to explore the benefits and combined effects of BRAF inhibition and stereotactic radiosurgery in melanoma brain metastasis. 45 The present study also compared brain metastasis with other extracranial metastatic tissue sites in the BRAF-WT, BRAF-V600 without BRAFi, and BRAF-V600 with BRAFi groups. Shoenewolf et al examined 83 stage IV melanoma patients and found similar patterns of metastases between BRAF-V600E and BRAF-WT patients.…”

Toxicity and efficacy of Gamma Knife radiosurgery for brain metastases in melanoma patients treated with immunotherapy or targeted therapy—A retrospective cohort study

“…However, the results regarding the effect of IT and TT on LCR are controversial. Recent studies reported no differences in the local tumor control of irradiated MBM among different IT/TT treatment groups or based on BRAF status 28,29 . Irrespective of the effect that modern oncological therapies seem to have on LCRs for MBM, the even more prominent question that has not been sufficiently addressed is about possible side effects of concurrent radiotherapy or radiosurgery and IT or TT.…”