- Recently published open access in the journal Nature Communications*, an invited Comment article first authored by VHIO’s Elena Garralda, sets out next steps toward validating the Immune RECIST (iRECIST) consensus guideline and highlights novel approaches in the development of response criteria for cancer immunotherapy.
The advent of cancer immunotherapy, spurred through the development of immune checkpoint inhibitors for several tumor types, undoubtedly represents a tremendous advance in oncology. However, many patients still do not respond to immunotherapy, which has led to the development of myriad novel immune-based treatments either as monotherapy or in combination with other agents.
In 2022 alone, there were over 4800 active clinical trials testing PD1/PD-L1 monoclonal antibodies as monotherapy or in combination, with many additional ongoing studies with other immune-based treatments including modified antibodies and cell therapies. Last year, there were 1800 active cell therapy trials and a total of 433 newly initiated cell therapy studies.
“In any drug development process, but especially with such a large number of potentially toxic agents in development in immuno-oncology, we must be able to decide early whether a novel treatment approach is active and therefore warrants further study,” says Elena Garralda, Executive Director of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, and co-Director of our Clinical Research Program.
In the early stages of drug development and based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria published in the year 2000, response surrogate endpoints including tumor response rate and progression-free survival are often used for assessing antitumor activity in advanced-stage disease. The application of immunotherapy has subsequently raised a new and important issue for response assessment of targeted therapies.
“The early detection of immunotherapy-induced tumor response in patients is often complicated by the development of a temporary pseudoprogression, which is an initial increase in tumor size or the appearance of new lesions, followed by stable disease or a response to therapy. This phenomenon could therefore cause premature treatment withdrawal when interpreted as progressive disease according to RECIST criteria,” adds Garralda.
Chaired by Elena Garralda alongside Scott A. Laurie at the Ottawa Hospital Cancer Centre (Canada), the role of the RECIST Working Group (RWG) is to ensure that RECIST criteria undergoes continued testing, validation and updating in parallel with advances in treatment approaches including cancer immunotherapy. In 2017, the RWG proposed a modified version of the RECIST 1.1—as the widely adopted standard criteria used in early clinical trials of novel agents for solid tumors—for immune-based therapies.
The Immune RECIST (iRECIST) criteria have since been incorporated as an exploratory endpoint into many immunotherapy trials to capture unusual patterns of response that can occur with these agents. The primary aim was to ensure consistent design and data collection, facilitate the ongoing collection of study data and ultimately validate the guideline.
In an invited Comment article published in Nature Communications*, co-authors Elena Garralda, Scott A. Laurie, Lesley Seymour at the Canadian Cancer Trials Group, Queens University and Cancer Centre of Southeastern Ontario, and corresponding author Elisabeth G. E. de Vries, Professor of Medical Oncology at the University Medical Centre Groningen in the Netherlands—both past Chairs of the RWG—briefly review progress to-date toward validating iRECIST. Five years after implementation, they suggest next-step actions and draw on recent studies incorporating novel approaches and technologies including radiomics and circulating tumor DNA in developing new response criteria for cancer immunotherapy.
Moving forward, the authors call for the sharing of clinical trial data from patients receiving immunotherapy in order to analyze results in aggregate, regardless of the specific therapy used, and without comparing agents. These analyses will be performed to confirm the utility of iRECIST as a surrogate endpoint in clinical trials to establish if iRECIST adds value to standard RECIST criteria.
“The incorporation of iRECIST into response criteria in a validated manner will require data sharing. By working together, iRECIST could potentially be adopted as the standard response assessment for cancer immunotherapy. We are also looking to include novel imaging and imaging analyses as well as circulating tumor DNA by liquid biopsy for response criteria,” concludes Elena Garralda, fist author of this present Comment article and Principal Investigator of VHIO’s Early Clinical Drug Development Group.
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Reference:
Garralda E, Laurie SA, Seymour L, de Vries EGE. Towards evidence-based response criteria for cancer immunotherapy. Nat Commun. 2023 May 24;14(1):3001.
