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Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery

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Abstract

Purpose

Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS.

Methods

49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan–Meier method.

Results

25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24 months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01).

Conclusion

In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.

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Data availability

Summary data supporting the results reported in this article can be requested by emailing the corresponding author.

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Acknowledgements

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Joseph D. Tang and Matthew N. Mills contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr. , Tampa, FL, USA

    Joseph D. Tang, Matthew N. Mills, Justyn Nakashima, Ammoren E. Dohm, Evan J. Wuthrick, Hsiang-Hsuan M. Yu, Daniel E. Oliver & Kamran A. Ahmed

  2. Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Nikhil I. Khushalani

  3. Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Peter A. Forsyth, Michael A. Vogelbaum & James K. C. Liu

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by JT, MM, JN, AD, and KA. The first draft of the manuscript was written by JT, MM, and KA. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kamran A. Ahmed.

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Competing interests

Joseph D. Tang: no disclosures. Matthew N. Mills: no disclosures.Justyn Nakashima: no disclosures.Ammoren E. Dohm: no disclosures.Nikhil I. Khushalani: personal consulting fees from Astra-Zeneca, Bristol Myers Squibb, Incyte, Iovance, Merck, Novartis, Nektar, Replimune, Regeneron, Jounce, Castle Biosciences, and Instill Bio; receives research funding from Bristol Myers Squibb, Merck, Novartis, Replimune, Celgene, Regeneron, HUYA Biopharmaceuticals, and GlaxoSmithKline; and has common stock holdings in Bellicum Pharmaceuticals, Amarin Corp, and Asensus Surgical. Peter A. Forsyth: has funding from Pfizer and Celgene and is on the advisory boards of Novocure, BTG, Inovio, AbbVie, Ziopharm, Tocagen, and Pfizer. Michael A. Vogelbaum: has indirect equity and royalty interests in Infuseon Therapeutics, Inc. and has received honoraria from Tocagen, Inc. and Celgene. Evan J. Wuthrick: has served on the advisory board and has received honoraria from Bayer, has received research funding from Bristol-Myers Squibb, and has intellectual property: cGMP as protector for chemotherapy and radiation. Hsiang-Hsuan Michael Yu: has received speaker’s honoraria from BrainLab and is on the advisory boards of Novocure and AbbVie. Daniel E. Oliver: no disclosures. James K.C. Liu: no disclosures. Kamran A. Ahmed: has received research funding from Bristol-Myers Squibb, Eli Lilly, and Genentech.

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Tang, J.D., Mills, M.N., Nakashima, J. et al. Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery. J Neurooncol 166, 431–440 (2024). https://doi.org/10.1007/s11060-023-04543-9

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