iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics

Abstract

Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden-a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline-iRECIST-was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.

Conflict of interest statement

Declaration of interests

LS reports grants from AstraZeneca and Merck, outside the submitted work. AP owns stocks in Merck & Co. RF reports personal fees from Amgen, Abbvie, Aptiv, Aragon, BMS, Bioclinica, Celldex, Celsion, Clovis, Covance, Biomedical systems, ACR Image Metrix, Exelixis, Genentech, Janssen, Kyowa, Loxo, ICON Medical Imaging, Eisai, EMD Serono, Imaging Endpoints, Mlrati, Celgene, Merck, Novartis, Novocure, Roche, Pfizer, Quintile, Tokai, ONO, Red Hill, Radiant Sage, Orbimed Advisors, Cinven, Virtualscopics, Sun Advanced Pharma Research Company, Median Therapeutics, Optimer Biotechnology Inc, Vascular Biogenics, Ignyta, Immunocellular CBT Pharmaceuticals, Tracon, DNAtrix, CytRx, Kolltan, and Samsung Bioepsis, outside the submitted work. LHS reports grants and consulting fees from Novartis, grants from Astellas, Eli Lilly, Merck, Pfizer, consulting fees from GSK, outside the submitted work. JD reports grants from Merck, AstraZeneca, Pfizer, Ottawa Hospital Research Institute, Novartis, outside the submitted work. FSH reports grants from Bristol-Myers Squibb, and personal fees from Merck, Novartis, Genentech, and EMD Serono, outside the submitted work. Additionally, FSH has a patent MICA Related Disorders with royalties paid, and a patent Tumor Antigens and Uses Thereof issued. JDW reports grants from Bristol Myers Squibb, Merck, and Genentech during the conduct of the study; consulting fees from Bristol Myers Squibb and Merck, and is on the scientific advisory board for Medimmune, outside the submitted work. MB reports personal fees from Genentech outside the submitted work, and owns stocks in Roche. CC reports personal fees from Roche, BMS, and AstraZeneca, outside the submitted work. EGEdV reports consulting fees from Synthon, Medivation, and Merck; and grants from Novartis, Amgen, Roche/Genentech, Servier, Chugai, Synthon, AstraZeneca, and Radius Health, outside the submitted work. JB, SM, NUL, SL, AC, PT, OSH, and LKS declare no competing interests.

Copyright © 2017 Elsevier Ltd. All rights reserved.

Figures

Figure 1. Process for developing and validating iRECIST consensus guidelines

Blue shaded boxes represent steps still in progress. RECIST=Response Evaluation Criteria in Solid Tumours.

Figure 2. RECIST 1.1 and iRECIST: an example of assessment

Prefix “i” indicates immune responses assigned using iRECIST; others without “i” are confirmed by RECIST 1.1. RECIST=Response Evaluation Criteria in Solid Tumours. iCR=complete response. iCPD=complete progression. iPR=partial response. iSD=stable disease. iUPD=unconfirmed progression. TP=timepoint.