Abstract
We developed and evaluated a method for making early predictions of best overall response (BOR) and overall survival at 6 months (OS6) in patients with cancer treated with immunotherapy. This method combines machine learning with modeling of longitudinal tumor size data. We applied our method to data from durvalumab-exposed patients with recurrent/metastatic head and neck cancer. A fivefold cross-validation was used for model selection. Independent trial data, with various degrees of data truncation, were used for model validation. Mean classification error rates (90% confidence intervals [CIs]) from cross-validation were 5.99% (90% CI 2.98%-7.50%) for BOR and 19.8% (90% CI 15.8%-39.3%) for OS6. During model validation, the area under the receiver operating characteristic curves was preserved for BOR (0.97, 0.97, and 0.94) and OS6 (0.85, 0.84, and 0.82) at 24, 18, and 12 weeks, respectively. These results suggest our method predicts trial outcomes accurately from early data and could be used to aid drug development.
© 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
Publication types
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Clinical Trial, Phase I
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Clinical Trial, Phase II
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Clinical Trial, Phase III
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Comparative Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / pharmacokinetics*
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized / administration & dosage
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Antibodies, Monoclonal, Humanized / pharmacokinetics
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Antibodies, Monoclonal, Humanized / therapeutic use
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Antineoplastic Agents, Immunological / administration & dosage
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Antineoplastic Agents, Immunological / pharmacokinetics*
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Antineoplastic Agents, Immunological / therapeutic use
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Drug Development
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Drug Therapy, Combination
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Female
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Head and Neck Neoplasms / pathology
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Humans
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Immunotherapy / methods*
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Machine Learning
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Male
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Middle Aged
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Neoplasm Recurrence, Local / drug therapy
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Neoplasm Recurrence, Local / mortality
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Predictive Value of Tests
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Squamous Cell Carcinoma of Head and Neck / diagnosis
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Squamous Cell Carcinoma of Head and Neck / drug therapy*
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Squamous Cell Carcinoma of Head and Neck / mortality
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Squamous Cell Carcinoma of Head and Neck / secondary*
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Survival Analysis
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents, Immunological
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durvalumab
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tremelimumab