Immunotherapies display novel response patterns that affect the design of imaging based studies and the subsequent evaluation of imaging data. Applying traditional chemotherapy-based response assumptions to immunotherapy trials can result in inaccurate interpretation of response, premature therapy termination, and unnecessary removal of subjects from a trial. Therefore, a thorough understanding of these response patterns and the new criteria used to assess them is critical for conducting a successful clinical trial for immunotherapy.
Today, a new consensus guideline was released—iRECIST – developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumors (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. These consensus guidelines will help to standardize and validate immune related criteria across all immunotherapy clinical trials
Some highlights of the new guideline include:
- Key questions raised by tumor response patterns specific to immunotherapy are assessed.
- iRECIST is based on RECIST 1.1. – Lesion Measurement, Baseline Lesion Size, Baseline Lesion Number remain unchanged.
- Measurable new lesions (now called new lesions target) are not incorporated into the total tumor burden.
- The major change is the concept of resetting the bar if progression according to RECIST 1.1 is followed at the next evaluation by tumor shrinkage.
- This approach allows atypical responses, such as delayed responses that occur after pseudoprogression, to be identified, further understood, and better characterized.
- A new overall response “unconfirmed progressive disease” (iUPD) is defined and corresponds to first RECIST 1.1 PD. iUPD requires confirmation, based on either a further increase in size (or in the number of new lesions) in the lesion category, or progression (defined by RECIST 1.1) in lesion categories that had not previously met RECIST 1.1 progression criteria. Treatment past PD and iUPD confirmation should only be considered if the patient is clinically stable. If iUPD could not be confirmed the reasons why should be recorded.
These guidelines are critical with the proliferation of immunotherapy clinical trials and the unprecedented number of trials planned to test new immune modulators. Median Technologies will soon have these new guidelines ready to implement for immunotherapy clinical trial image analysis.
Read more in The Lancet Oncology – http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30074-8/fulltext
Dr. Nathalie Faye, Medical Director, Median Technologies
Dr. Robert Ford, Founder and Principal, Clinical Trials Imaging Consulting, LLC
Co-Author “iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics” The Lancet Oncology, Volume 18, No. 3, e143–e152, March 2017