Michael A. Postow, MD
The standards for reporting findings from immunotherapy studies should reflect the unique efficacy and toxicity characteristics of this rapidily emerging modality, with detailed and transparent explanations of definitions, according to a panel of experts.
The panel developed 12 recommendations for improving the reporting of data from immunooncology (IO) trials which are detailed in a joint report from the American Society of Clinical Oncology (ASCO) and the Society for Immunotherapy of Cancer (SITC).
The Trial Reporting in Immuno-Oncology (TRIO) statement was recently published in both the Journal of Clinical Oncology
and the Journal for ImmunoTherapy of Cancer
“The IO field is moving so fast with many agents in development,” said senior author Michael A. Postow, MD, of Memorial Sloan Kettering Cancer Center. “The TRIO guidelines are intended to help standardize our understandings of the benefits and risks of each agent in the published literature.”
The recommendations were developed starting in 2016 by a working group of members of ASCO and SITC that included medical oncologists, clinical researchers, biostatisticians, and immunologists, as well as government and industry members. The 12 recommendations are grouped under efficacy data, toxicity information, or details about combination therapies. The recommendations are listed here verbatim as bullet points.
Standards for Efficacy Reporting
• Report the criteria used to evaluate response to therapy and the rationale for the selected criteria
Most clinical trials use the Response Evaluation Criteria in Solid Tumors (RECIST) standards to categorize the efficacy of oncology drugs. Although these specifications have been sufficient for the evaluation of other types of chemotherapy, IO therapies have unique early tumor responses that may be misinterpreted as disease progression. To address this challenge, new criteria have been developed by multiple groups. Although these new criteria are all designed to improve the evaluation and optimize the benefit of IO therapies, no single set has been universally adopted.
The working group does not recommend 1 particular set of criteria, instead stating that it is critical to clearly state which response criteria were used for evaluation and if the criteria were specified before the study was done. There is also a recommendation for investigators to discuss why the chosen criteria were selected. For consistency and comparability across all clinical trials, the recommendations suggest continuing to report the RECIST criteria–based evaluation along with the chosen IO-specific analyses.
• Include spider plots or swimmer plots in efficacy descriptions to better report kinetics of response for nonrandomized trials
Waterfall plots are often used to display trial efficacy data, but the workgroup argues that these types of figures leave out key temporal data that can be important for evaluating the efficacy of a therapeutic. Spider plots show tumor burden over the course of treatment for each patient in a trial. Swimmer plots are useful because they show the duration and onset of response in relation to the time of treatment administration (Figures 1 and 2
One limitation that is noted for the use of spider plots is that data from trials with large numbers of patients can result in plots that are difficult to interpret. Because of this, spider plots are specifically recommended for displaying the results of smaller trials. Additionally, these plots can be useful for displaying interesting results within a subset of patients from a larger trial. Spider plots are recommended for use in addition to waterfall plots.
• Report how disease control rate is defined and how its components are assessed
Composite endpoints, such as “disease control” and “clinical benefit,” can be determined using variable, nonstandardized criteria. To ensure the clarity of the trial methods and the correct interpretation of data, the criteria for these endpoints must be clearly described, including the timing and methods used to assess the criteria. This includes specifically stating the definition of “baseline,” what criteria designate an “event,” and what information is considered to be censored.
• Report criteria that allow patients to continue treatment beyond disease progression
Pseudoprogression is a phenomenon that has been observed in patients receiving IO treatment. In these cases, a patient’s tumor response manifests as an initial increase in lesion number that is followed by a clinical response. Although typical clinical trials cease treatment if a patient exhibits progressive disease, because of the potential for pseudoprogression, patients in IO clinical trials are often permitted to continue receiving therapy despite initial disease progression.