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Leptomeningeal Metastases: New Opportunities in the Modern Era
Jessica A Wilcox1, Min Jun Li2, Adrienne A Boire3,4
1Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
Leptomeningeal metastases arise from cancer cell entry into the subarachnoid space, inflicting significant neurologic morbidity and mortality across a wide range of malignancies. The modern era of cancer therapeutics has seen an explosion of molecular-targeting agents and immune-mediated strategies for patients with breast, lung, and melanoma malignancies, with meaningful extracranial disease control and improvement in patient survival. However, the clinical efficacy of these agents in those with leptomeningeal metastases remains understudied, due to the relative rarity of this patient population, the investigational challenges associated with studying this dynamic disease state, and brisk disease pace. Nevertheless, retrospective studies, post hoc analyses, and small prospective trials in the last two decades provide a glimmer of hope for patients with leptomeningeal metastases, suggesting that several cancer-directed strategies are not only active in the intrathecal space but also improve survival against historical odds. The continued development of clinical trials devoted to patients with leptomeningeal metastases is critical to establish robust efficacy outcomes in this patient population, define drug pharmacokinetics in the intrathecal space, and uncover new avenues for treatment in the face of leptomeningeal therapeutic resistance.
Insights
New cancer therapies show promise for leptomeningeal metastases (cancer spread to the brain and spinal cord fluid). Despite challenges, these treatments are active in the intrathecal space and improve survival.
Area of Science:
- Neuro-oncology
- Cancer Therapeutics
- Metastatic Disease
Background:
- Leptomeningeal metastases (LM) cause significant neurological damage in various cancers.
- Modern cancer treatments like targeted therapy and immunotherapy improve survival for extracranial disease.
- The efficacy of these advanced therapies in LM patients is understudied due to rarity and research challenges.
Purpose of the Study:
- To review the current evidence on the efficacy of modern cancer-directed strategies in patients with leptomeningeal metastases.
- To highlight the challenges and opportunities in studying LM treatment.
- To emphasize the need for dedicated clinical trials in this population.
Main Methods:
- Review of retrospective studies, post hoc analyses, and small prospective trials over the last two decades.
- Analysis of data concerning the activity of cancer-directed strategies in the intrathecal space.
- Evaluation of survival outcomes in LM patients treated with novel agents.
Main Results:
- Evidence suggests that several cancer-directed strategies are active within the intrathecal space.
- These novel treatments appear to improve survival for leptomeningeal metastases patients compared to historical controls.
- Despite challenges, a glimmer of hope exists for improved outcomes in this patient group.
Conclusions:
- Dedicated clinical trials are critical for establishing robust efficacy of cancer-directed strategies in leptomeningeal metastases.
- Further research is needed to define intrathecal drug pharmacokinetics and overcome therapeutic resistance.
- Continued investigation holds promise for improving outcomes in patients with leptomeningeal metastases.
