Real World Outcomes of Melanoma Brain Metastases Treated with Immunotherapy with or without Stereotactic Radiosurgery Open Access

Kleber, Troy (Spring 2022)

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Background: Immunotherapies (IT) are effective for melanoma with extracranial metastases based on multiple phase 3 clinical trials. For patients with melanoma brain metastases (MBM), however, the role of IT is less clear. We hypothesized that treatment of MBM with IT and SRS in combination results in longer patient survival compared to IT alone.

Methods: Using the National Cancer Database, we identified 775 adult patients diagnosed with MBM between 2010 and 2017 treated with IT. We excluded those who received whole-brain radiotherapy. We then compared receipt of both IT and SRS (IT/SRS) vs. IT alone (IT/noSRS). Our primary endpoint was overall survival (OS). As a subset analysis on the IT/SRS cohort, we assessed the association between the relative timing of therapies and OS. This involved multiple statistical analyses using different definitions for relative timing: days from start of SRS to IT, proximity of therapies (IT started ≤ 28 vs. > 28 days from SRS), and sequence of therapies (IT started after vs. before SRS). Adjusted hazard ratios (aHR) were calculated using multivariable Cox regression modeling and reported with 95% confidence intervals (CI). Significance level was set as 0.05.

Results: Of the 775 adult patients with MBM treated with IT, 546 (70.5%) were male, 759 (98.3%) were white, and 654 (84.4%) were diagnosed in 2014-2017. Those with lung, liver, and bone metastasis numbered 275 (56.9%), 100 (20.6%), and 84 (17.4%), respectively. 492 (63.5%) patients were treated with IT/SRS, and 283 (36.5%) received IT/noSRS. The median OS was 29.5 months (95% CI: 22.3 - 44.8 mo) for IT/SRS and 11.9 months (95% CI: 9.2 - 17.2 mo) for IT/noSRS with an aHR of 0.70 (95% CI: 0.56-0.88, p < 0.01). For the IT/SRS cohort, there was no significant association between the relative timing of therapies and OS.

Conclusions: Patients with MBM treated with both IT and SRS appear to have longer survival compared to IT without intracranial radiation. This finding demonstrates the benefits of local therapy for brain metastases when prescribed in combination with IT.

Table of Contents

Introduction 1

Methods 2

Results 6

Discussion 16

Conclusion 22

Bibliography 23

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