Clinical Validation of Mathematically Derived Early Tumor Dynamics for Solid Tumors in Response to Durvalumab

Qin Li, Vittorio Cristini, Ashok Gupta, Ikbel Achour, J. Carl Barrett, Eugene J. Koay

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Early prediction of response to immunotherapy may help guide patient management by identifying resistance to treatment and allowing adaptation of therapies. This analysis evaluated a mathematical model of response to immunotherapy that provides patient-specific prediction of outcome using the initial change in tumor size/burden from baseline to the first follow-up visit on standard imaging scans.METHODSWe applied the model to 600 patients with advanced solid tumors who received durvalumab in Study 1108, a phase I/II trial, and compared outcome prediction performance versus size-based criteria with RECIST version 1.1 best overall response (BOR), baseline circulating tumor (ct)DNA level, and other clinical/pathologic predictors of immunotherapy response.RESULTSIn multiple solid tumors, the mathematical parameter representing net tumor growth rate at the first on-treatment computed tomography (CT) scan assessed around 6 weeks after starting durvalumab (α1) had a concordance index to predict overall survival (OS) of 0.66-0.77 on multivariate analyses. This measurement of early tumor dynamics significantly improved multivariate OS models that included standard RECIST v1.1 criteria, baseline ctDNA levels, and other clinical/pathologic factors in predicting OS. Furthermore, α1 was assessed consistently at the first on-treatment CT scan, whereas all traditional RECIST BOR groups were confirmed only after this time.CONCLUSIONThese results support further exploring α1 as an integral biomarker of response to immunotherapy. This biomarker may be predictive of further benefit and can be assessed before RECIST response groups can be assigned, potentially providing an opportunity to personalize oncologic management.

Original languageEnglish (US)
Article number00074
Pages (from-to)e2300254
JournalJCO clinical cancer informatics
Volume8
DOIs
StatePublished - Jul 2024

Keywords

  • Models, Theoretical
  • Prognosis
  • Tomography, X-Ray Computed/methods
  • Immunotherapy/methods
  • Humans
  • Middle Aged
  • Antibodies, Monoclonal/therapeutic use
  • Neoplasms/drug therapy
  • Male
  • Treatment Outcome
  • Tumor Burden
  • Antineoplastic Agents, Immunological/therapeutic use
  • Female
  • Aged

ASJC Scopus subject areas

  • General Medicine

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