Melanoma Brain Metastases in the Era of Targeted Therapy and Checkpoint Inhibitor Therapy.

John M Rieth,Brooke Jennings,Jeremy D Greenlee,Mario Zanaty,Yousef Zakharia,Michael D Henry,Marion Vanneste,Aaron D Bossler,Mohammed M Milhem,Umang Swami,Sarah L Mott

doi:10.3390/cancers13071489

Abstract

Simple SummaryBrain metastases are common in melanoma and are often associated with significant morbidity and mortality. Although many new treatments for melanoma have been approved in recent years, including immune checkpoint inhibitors and BRAF/MEK inhibitors, limited data are available for survival for patients with brain metastases treated with these novel therapies. The aim of this retrospective study was to evaluate current surgical, radiation, and systemic therapies over the past 10 years in melanoma patients with brain metastases. Our study noted increased overall survival in patients treated with craniotomy and CTLA-4 checkpoint inhibitors, while whole brain radiation was associated with poorer overall survival.Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.

Highlights

Of all malignancies, melanoma has the highest propensity to migrate to the brain, which is associated with a poor prognosis [1,2,3]
Identification of a primary site and/or formal dermatology consultation for evaluation of a primary melanoma was conducted in 189 patients
We present a cohort of 209 melanoma patients with intracranial metastases

Summary

Introduction

Melanoma has the highest propensity to migrate to the brain, which is associated with a poor prognosis [1,2,3]. The frequency of brain metastases in melanoma is thought to be on the rise due to the increased survival of patients diagnosed with melanoma. Patients with melanoma had limited treatment options, including chemotherapy, wholebrain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgical resection. Since 2011, checkpoint inhibitors and BRAF/MEK targeted therapy have revolutionized the treatment of melanoma, resulting in dramatically enhanced survival. The first single-agent BRAF inhibitors were approved in 2011, single-agent ipilimumab in 2011, PD-1 inhibitors in 2014, and combination ipilimumab and nivolumab in 2015

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