In 2017, Merck was granted approval for Keytruda, a cancer drug that marked a first for the Food and Drug Administration. Previously, all oncologic products had been approved based on their ability to treat cancer at a tumor site. However, Keytruda was approved because of its ability to treat a lesion based on a biomarker where the tumor originated.
Historically, physicians identified cancers by their anatomical location, which makes sense because without superior imaging or a biomarker, there was no other option than to rely on anatomy for describing the tumor type. But now advanced biomarker methods can be used to track tumor status over time. More information can be found on the FDA website.
A Big Change for Oncologists
Tumors can show over-expression of receptors and biochemical signaling agents. The same over-expression can occur on different tumors in the same or different anatomical locations. As a result, most chemotherapy agents and anti-angiogenesis agents are designed to “blast the tumor” (and the body) with an agent that destroys tissues in a broad manner.
The new method approved by the FDA uses a “personalized medicine” approach. Now, with the use of biomarkers, targeted lesions with specific receptors can be identified regardless of anatomical location.
The Challenge to Medical Imaging Teams
RECIST 1.1 and even iRECIST are designed to assimilate a specific anatomical tumor profile and identify tumor response. With the new therapies in development, read systems must be developed (and are being developed) to handle multiple RECIST-type reads in a single image read. In other words, subjects will be enrolled based on the biomarker, and the reads conducted with the read system that best supports the anatomical location of the lesions.
For example, RECIST 1.1 might be employed in a pancreatic tumor location while the Choi criteria may need to be utilized in subjects presenting GIST tumors. Alternatively, situations might arise where a trial necessitates multiple response criteria assessments on the same lesion measurements (e.g., RECIST 1.1, irRC, etc.). Understanding how best to design and operationalize an oncology trial that includes are more sophisticated approach to imaging will be key to regulatory success.
The complexities of the read and the resulting statistics will be interesting to follow. The reads have been successful with Keytruda. It’s now a matter of time to see if and how other agents do the same.
Manual, outdated imaging based on paper case report forms (CRFs) and one-size-fits-all workflows cause compliance and data quality issues throughout oncology clinical trials.
Learn how ERT’s imaging solution combines deep scientific and regulatory expertise with tools, workflows, scoring criteria, software-guided reads and automated measurements adapted to tumor types so you can seamlessly– and securely – collect, evaluate, manage and report high quality, objective imaging endpoint data in oncology trials. Click here for more information.
Dr. Joe Pierro is with ERT’s Scientific Affairs group.