Clarifying the Criteria That Better Capture Anti-Tumor Activity of Immune Therapeutics

August 3, 2017 Oliver Bohnsack

The field of immunotherapy and the treatment promise of checkpoint inhibitors have brought a new level of optimism to oncologists and cancer patients. We have made important strides in clarifying criteria for more reliable and reproducible assessment data in targeted immunotherapy and oncology studies.

Toward consistency in following RECIST

Currently, the majority of clinical trials evaluating cancer treatment for objective response in solid tumors use RECIST (Response Evaluation Criteria in Solid Tumors). These rules are highly dependent upon measurement and interpretation of tumors and their metastases.

However, with the ever-increasing complexity of cancer trials, involving dozens or even hundreds of investigators, different clinicians may vary greatly in their methods or skills for performing these assessments. Consistency in following the imaging requirements and rules, and the interpretation of findings on CT or MRI scans, is even more challenging. When investigators vary in how they follow RECIST to determine trial endpoints such as delay of progress or rate of responders to a treatment, patients' evaluations – and as such, the study results – may be placed in jeopardy.

In 2009, PAREXEL co-published Immune-related Response Criteria (irRC), based on World Health Organization (WHO) criteria (irRC, Wolchok, et. al. 2009. Clin Cancer Res 15:7412-20), with the aim of better assessing the effect of immunotherapeutic agents. Then, Nishino et. al. published two papers in 2013 (Clin Cancer Res. 2013 Jul 15;19(14):3936-43) and 2014 (Journal for ImmunoTherapy of Cancer2014; 2:17), in which she verified that:

  1. Unidimensional measurement following RECIST definitions is just as reliable.
  2. Five lesions serve the same purpose as 10 target lesions.

Mitigating ambiguity

Based on these publications, we were then challenged to implement this new paradigm of irRECIST into our clients' immune inhibition trials. So we found several aspects that needed clarification and more precise definition – and we are still finding more as we advance. In short, our intent is to mitigate the present ambiguity by clarifying the criteria that better capture antitumor activity of immune therapeutics, which may show a delayed onset of response to treatment.

The primary adaption of the existing immune-response criteria lies in the assessment of all detected lesions – those present at baseline and those growing or appearing additionally and new throughout the treatment. However, key modifications also address the following to better match clinical situations where patients may get worse before they get better:

  • More precisely define measurements for target lesions selected at baseline and especially for new lesions at follow-up.
  • Better define criteria for non-target lesions and allow that these may trigger progress as well, not just measured lesions.
  • Address the challenge of whether a progress must have or can have a subsequent second progression confirmation CT or MRI scan at least four weeks later.
  • Provide guidance to consistently evaluate patients who do not present with measurable lesions at study entry, then develop those that subsequently shrink.

Our hope is that consistent implementation of irRECIST by both investigators and blinded independent readers will help to provide patients with the best treatment available for their cancer, and avoid taking them off treatment too early or too late. We aim as well to reduce site-central discordance.

Read the full publication, “Adaptation of the Immune-Related Response Criteria” here.

Oliver Bohnsack, Senior Director, Medical Affairs
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