Abstract
The response assessment in neuro-oncology (RANO) working group recently proposed standardized response criteria for brain metastases (RANO-BM). We sought to compare RANO-BM to other criteria in an ongoing brain metastasis trial. The first 36 patients enrolled on NCT02085070, an ongoing trial of pembrolizumab for patients with untreated brain metastases, were included in this analysis. As RANO-BM had not been proposed when the protocol was written, response on trial was assessed using an institutional modification of RECIST 1.1 (mRECIST), wherein minimum target brain lesion size was 5 mm in longest diameter and up to five target brain lesions were followed. We here additionally assessed response using standard RECIST 1.1, RANO high-grade glioma (RANO-HGG), and RANO-BM. Comparison between the four criteria sets using cases eligible across the board revealed excellent concordance (kappa statistic > 0.8), with only one discordant case. However, compared to RECIST 1.1 or RANO-BM, using a 5 mm threshold for target brain lesions in mRECIST allowed enrollment of 13 additional patients, five of whom had durable responses. Compared to RANO-HGG, 19 additional patients were enrolled using mRECIST, eight of whom had durable responses. Consequently, this resulted in response rates ranging from 12% with RANO-HGG to 28% with mRECIST. This study supports using a 5 mm threshold for target brain lesions when using high resolution MRI with ≤2 mm slices to facilitate accrual to similar clinical trials and provide earlier access to novel therapies for brain metastasis patients. Concordance among the four criteria studied was otherwise very high.
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Funding
This analysis did not receive any funding support. NCT02085070 received funding support from Merck and the Yale Cancer Center, but these funders did not have a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation of the manuscript; or decision to submit the manuscript for publication. Merck was involved in review and approval of the manuscript.
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JMQ reports funding from the NIH-NCATS CTSA-TL1 Medical Student Research Fellowship outside the submitted work. JBY reports funding from twenty-first Century Oncology outside the submitted work. SBG reports grants from Merck during the conduct of this study, and grants from AstraZenenca and personal fees from Clovis outside the submitted work. HMK reports grants from Merck during the conduct of this study, and consulting fees from Regeneron, Bioclinica, Alexion, and Prometheus outside the submitted work. No other disclosures are reported.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Jack M. Qian and Amit Mahajan have contributed equally to this work.
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Qian, J.M., Mahajan, A., Yu, J.B. et al. Comparing available criteria for measuring brain metastasis response to immunotherapy. J Neurooncol 132, 479–485 (2017). https://doi.org/10.1007/s11060-017-2398-8
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DOI: https://doi.org/10.1007/s11060-017-2398-8