Measuring response in a post-RECIST world: from black and white to shades of grey

Abstract

The unprecedented pace of therapeutic development in oncology has created a climate in which the traditional methods of evaluating agent activity might no longer be adequate. How is the field transitioning to new endpoints in early drug development and what are the difficulties in this transition? Here, we will explore the historical context for the current criteria for tumour response evaluation and some of the pitfalls in using these standards when testing newer anticancer agents for activity. We will argue that the current drug development environment dictates different outcome measurements and therefore more imaginative and rigorous early-phase trial designs.

Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients

“…Pathologic examination of metastases resected after Ipilumimab infusion indicate that this unusual course may reflect pronounced inflammation and edema induced by tumor-infiltrating lymphocytes. This profile of therapeutic activity is not adequately captured by the current RECIST criteria for monitoring tumor response, which primarily are based on target lesion volume (33). Thus, although overall survival remains the most important parameter of clinical efficacy, the adoption of new indexes that incorporate recent insights into the concept of immune equilibrium should be strongly considered (34).…”

A phase II study to determine the ability of gefitinib to reverse fluoropyrimidine resistance in metastatic colorectal cancer (the INFORM study)

“…Response Evaluation Criteria in Solid Tumours (RECIST) (Michaelis and Ratain, 2006) was used to assess objective tumour response by computerised tomography scan at baseline and then after every 8 weeks until progression. Toxicities were assessed by National Cancer Institute Common Toxicity Criteria (CTC) version 2.0 every 2 weeks.…”

Evaluating the activity of temsirolimus in neuroendocrine cancer

“…This trial exemplifies the difficulty of interpreting the results of single-arm trials using the RECIST criteria (Michaelis and Ratain, 2006). This is especially true for noncytotoxic agents being studied in indolent diseases for which one would expect a high rate of stable disease in the absence of treatment.…”