New ASCO/SITC Guidance Addresses Shortcomings of Immuno-Oncology Trial Reporting

The American Society of Clinical Oncology (ASCO) and the Society for Immunotherapy of Cancer (SITC) recently issued recommendations on Trial Reporting in Immuno-Oncology (TRIO). The aim of the TRIO recommendations is to enhance the understanding and comparison of efficacy and toxicity outcomes in immuno-oncology trials, as well as the combination and sequencing of treatments.

“The TRIO recommendations are intended to improve the reporting of immuno-oncology clinical trials and thus provide more complete evidence on the relative benefits and risks of an immuno-oncology therapeutic approach,” wrote the authors, led by Apostolia M. Tsimberidou, MD, PhD, a professor in the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center.

Compared with other guidelines, the TRIO recommendations are more prescriptive and promote the interpretation and comparison of different immune-oncology trials to facilitate trial conduct and relevant data collection.

“The TRIO recommendations provide a good framework to report results on the increasing number of immune-oncology trials-especially in the combination realm,” said Shivaani Kummar, MD, professor of oncology and radiology at Stanford University School of Medicine, in an exclusive interview with Cancer Network. “It’s important that we attempt to standardize how these trials are reported, and for the reports to have enough information about efficacy; incidence of pseudoprogression; the timeline, onset, and management of side effects; and whether the management of side effects compromises the efficacy of the agent or agent(s).”

Dr. Kummar explained that the controversial topic of pseudoprogression refers to inflammation of the tumor. Tumor lesions can look worse on scans due to inflammation, and this presentation does not necessarily reflect true tumor growth.

“We need to get a better handle on what is the true incidence of pseudoprogression in patients on immune-oncology combinations, which patients will likely develop pseudoprogression, and how to optimally manage it so that patients who have true disease progression do not get unnecessarily treated by continuing the immuno-oncology agent in the hope that it is pseudoprogression.”     

The TRIO recommendations were formulated using input from a working group convened by ASCO and SITC in fall 2016 consisting of medical oncologists, immunologists, clinical researchers, biostatisticians, and industry and government stakeholders. The TRIO recommendations are rooted in expert consensus due to a paucity of evidence-based data.

The following is a verbatim list of the 12 TRIO efficacy reporting standards:

1. Report the criteria used to evaluate response to therapy and the rationale for the chosen criteria.

2. Include spider plots or swimmer plots in efficacy descriptions to better report kinetics of response.

3. Report how disease control rate is defined and how its components are assessed.

4. Report criteria that allow patients to continue treatment beyond disease progression.

5. Report the number (proportion) of patients who are treated beyond progression, treatment beyond progression duration, emergence of new toxicity, and efficacy after initial progression.

6. Report progression-free survival and overall survival using Kaplan-Meier analyses.

7. Differentiate between the clinical diagnoses of IO toxicity and the specific symptoms that led to the diagnoses.

8. If the prespecified clinical diagnoses used in data collection belong to categories such as “immune-related adverse events” or “adverse events of special interest,” report how these terms are defined and why these categories were selected for trial reporting.

9. Report all toxicity by specific grade.

10. Report clinical interventions used to manage IO toxicity.

11. Report time of onset and duration of IO toxicity.

12. Report the scientific hypothesis for the combination or sequence on the basis of preclinical and/or clinical data as well as the rationale for the selection of the particular dose(s) and sequence of agents.

Of note, recommendations 1, 2, 3, 4, 5, 7, 8, 9, 10, and 11 pertain only to immuno-oncology therapies.

The researchers concluded that, because of the burgeoning nature of immuno-oncology clinical trials and the emergence of more evidence, these recommendations require regular revision.