Perceptive’s Dr. Oliver Bohnsack is considered one of the leading industry experts on oncology-imaging trial design and response criteria, having co-authored the immune-related response criteria (irRC, 2009), authored irRECIST (2014), and co-authored Comparison of Assessments using RECIST and irRECIST by Eggleton P. et al. (2020).
Here we discuss with Dr. Bohnsack the implications of these response assessments, based on his contribution as a co-author of the 2022 paper, and what they mean for oncology research and treatment decision-making moving forward.
Q: Can you give us some background on how cancer treatment response is currently measured in clinical trials?
Response Evaluation Criteria In Solid Tumors (RECIST) is a set of published rules that define when cancer patients improve (“respond”), stay the same (“stable”) or worsen (“progression”) during treatments. The original RECIST was published in February 2000 by an international collaboration, the RECIST working group, and updated to RECIST 1.1 in 2009.
Today, most clinical trials with imaging-based response or progression as an endpoint evaluating cancer treatments in solid tumors are using RECIST 1.1.
Meet with Dr. Bohnsack at IO360 2025 and attend his session, “I resist iRECIST!” to learn more. March 24-26 | Boston.
Q: Are there limitations to using RECIST 1.1 for tumor assessment?
Yes, there are. Patients treated with immune checkpoint inhibitors (ICIs), or any other form of immune-based treatment may experience pseudoprogression, which shows – at least on imaging – a tumor burden worsening, a growth or increase, before the treatment shows efficacy in and is visible on scans. In this situation these patients will be classified as progressive disease (PD) by RECIST V.1.1 and thus could lead to inappropriate and unfair treatment discontinuation.
The irRECIST approach allows responses not typically observed in traditional systemic treatments to be identified and better documented. The guideline describes a standard approach to solid tumor measurement and definitions for objective change in tumor size which can be used not only in immunotherapy clinical trials. Where any new lesion seen with RECIST 1.1 defines a treatment failure with documented PD, irRECIST allows for a possible continuation and further evaluation taking new lesions and the whole tumor burden into consideration.
Q: Can you tell us about the current findings outlined in the 2022 paper you contributed to?
Working with researchers from Merck Healthcare KGaA and renown clinical institutions we pooled data from 1765 patients with 12 types of advanced solid tumors treated with avelumab (an anti-programmed death ligand 1 (PD-L1) monoclonal antibody) monotherapy in the JAVELIN Solid Tumor and JAVELIN Merkel 200 trials, conducted a comparative analysis of tumor assessments by investigators according to RECIST 1.1 and irRECIST, and evaluated the correlation between progression-free survival (PFS), continued patient benefit and overall survival (OS).
The use of irRECIST identified a subset of patients with a best overall response (BOR) of progressive disease by RECIST 1.1 but an irBOR by irRECIST with a distinctive survival curve, thereby providing more clinically relevant information and better treatment decision-making options than RECIST 1.1 alone.
The publication demonstrates the benefit to a subgroup of patients in each of its various analyzed tumor indications, who otherwise would have foregone treatment and survival benefit when relying solely on RECIST 1.1 instead of irRECIST.
“In my opinion irRECIST easily can and shall replace outdated RECIST 1.1 on all solid tumor trials going forward.” – Dr. Oliver Bohnsack, VP, Medical Imaging, Perceptive
Q: What are the implications for sponsors of I-O trials who use RECIST 1.1 for evaluating response to treatment in studies of solid tumors?
Because immune-targeted treatment can initially cause the tumor burden to look as if it is progressing, when in fact it is not, trial sponsors using RECIST 1.1 to assess treatment response may end up having patients discontinued who would otherwise remain in the study. Using RECIST 1.1 could limit sponsors and investigators from recognizing the full treatment benefit of new therapies in development, and more importantly, may prevent patients from receiving potentially beneficial treatments.
Q: What can we expect moving forward, as the industry considers these findings and their implications?
Sponsors and regulatory agencies will have to consider whether based on this data RECIST 1.1 is still appropriate to be used and advocated for as the current assessment standard for physicians, aiding them in treatment decision making and whether to continue or discontinue the current immune oncology treatment of their patients. irRECIST includes and covers all that’s embedded in RECIST 1.1 already but now takes the entire tumor burden including new tumor growth into consideration. In my opinion irRECIST easily can and shall replace outdated RECIST 1.1 on all solid tumor trials going forward.
Dr. Bohnsack works closely with sponsors to optimize their medical imaging components of clinical oncology trials and helps their development programs succeed.
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