Alexander M. Castellino, PhD

April 19, 2016

NEW ORLEANS — A second-generation microdevice designed to be implanted into tumors has the ability to determine which of the 100 therapeutic choices (single agent or combination) contained in the device has the best antitumor activity.

Preclinical data for the device were presented here at the American Association for Cancer Research (AACR) 2016 Annual Meeting.

"The first human study has been initiated in patients with triple-negative breast cancer," presenter Oliver Jonas, PhD, a postdoctoral fellow at the Massachusetts Institute of Technology, Cambridge, Massachusetts, told Medscape Medical News. "Last year we published our results with the first-generation microdevice that tested 16 different therapies. We've increased the number to 100 per tumor with this much smaller device," he said.

In the first human study, a clinical trial in triple-negative breast cancer patients is testing the safety and feasibility of this approach.

"Currently, there are about 150 cancer drugs approved by the US Food and Drug Administration, and many cancer patients have different drugs to choose from to treat their specific disease. However, patients respond differently to different drugs, and often, no two patients have the same response to a specific drug," Dr Jonas said in an AACR press release.

Dr Oliver Jonas

"It has been a major challenge to determine which drug or combination of drugs to give to which patient. Being able to identify the right therapy that will work optimally for every patient will be a major advance," he added.

Dr Jonas explained that the cylindrical device, made of biocompatible plastics, is 700 microns in diameter and fits into a 20-gauge biopsy needle that directs it to the tumor site, where it is implanted. Reservoirs within the device are loaded with a drug or drug combinations, which are released at the tumor site. Drugs are released at a rate to match the concentration achieved with a standard delivery system.

After 24 hours, the implant is extracted along with a layer of surrounding tissue. The tissue is processed using standard histology and immunohistochemistry for standardized markers of apoptosis and proliferation to see if the drug works.

"During processing, the orientation of the device is maintained so we know where we loaded each therapy," Dr Jonas said.

He indicated that the microdevice has been successfully tested in a variety of tumors that had been grafted into mice, including those of the breast, ovaries, pancreas, and prostate, as well as melanoma.

Dr Jonas pointed out that through real-time imaging using fiber optics attached to each reservoir, they are also able to study the tumor at different time points.

"We are now able to measure how tumors adapt and change when they are treated locally or systemically and how their sensitivity to different drugs changes when switched from standard-of-care therapy," Dr Jonas said.

He explained that their approach allows them to take into account the microenvironment of the tumor to screen 100 drug and drug combinations efficiently and rapidly.

The first human trial in triple-negative breast cancer has enrolled four patients eligible for neoadjuvant therapy. Three devices were implanted in different locations and are testing eight different therapeutic choices at six locations. All are standard-of-care combinations for triple-negative breast cancer.

After the device has been removed, patients will undergo systemic therapy. In a retrospective analysis, responses to systemic therapy will be correlated with the device readout, Dr Jonas explained.

The researchers will soon be testing the safety and feasibility of this approach in patients with ovarian cancer.

The study was funded by the National Institutes of Health and the Koch Institute Frontier Research Program. Dr Jonas has disclosed no relevant financial relationships.

American Association for Cancer Research (AACR) 2016 Annual Meeting: Abstract 4381, presented April 19, 2016.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....