March 28, 2016

Research efficiency

The national I-SPY2 clinical trial, designed to evaluate several breast cancer drugs at once, 'graduates' its first three medications

There were no gowns, mortarboards, or long speeches, but Douglas Yee, M.D., still felt a sense of great accomplishment when three drugs recently “graduated” from the I-SPY2 clinical trial—proving effective enough to warrant further study.

Launched in 2010, the multicenter study was designed to compare the effectiveness of several breast cancer medications simultaneously. Yee, who directs the Masonic Cancer Center, University of Minnesota, also coleads the national committee in charge of selecting drugs for the trial.

The I-SPY2 trial is unique among clinical trials. Typically, a clinical trial examines one drug at a time and often involves five years or more of collecting data—followed by another five years or so to analyze the treatment’s effectiveness. In the I-SPY2 trial, multiple drugs are approved for testing simultaneously. Additionally, each participant’s tumor is profiled according to its molecular signature and then matched with the drug that researchers believe will be most effective in treating it.

Typically, women with breast cancer receive chemotherapy after surgery. In the I-SPY2 trial, women first receive the standard-of-care chemotherapy and may also receive another drug—and then surgery. The goal is to increase “pathologic complete responses,” Yee says, or total elimination of the tumor when examined by a pathologist.

The trial has tested roughly 15 chemotherapy drugs since it started. Medications are evaluated after they’ve been in use for six months, and the least effective medications are dropped from the study. Six drugs are currently being tested in the 17-site trial.

So far, Yee says, the “graduated” drugs have doubled the chances of participants achieving that “pathological complete response”—suggesting that the new drugs are improving responses to the standard-of-care treatment.

U of M chemistry professor Lee Penn, Ph.D., was diagnosed with triple negative breast cancer, a particularly aggressive form of breast cancer, in July 2011. When her surgeon recommended she become involved with the I-SPY2 study, Penn signed up.

“It seemed like a way to make some kind of positive contribution in the face of a horrible situation,” she says.

After her treatment, doctors found no live cancer cells in Penn’s tissue. “It was the best result you could possibly hope for,” she says. “I’m really lucky, right? I not only have excellent health care, but I’m right here on campus, one of the home sites for the I-SPY2 trial.”

Yee finds the many positive outcomes he’s seeing encouraging. And he’s particularly pleased with the speed of the trial: “To me, it demonstrates that we can identify active agents that are effective in the treatment of breast cancer in a much shorter timeline.”

The study—assisted by the Masonic Cancer Center’s Clinical Trials Office, which is supported by Minnesota Masonic Charities—also confirms what many researchers have been finding: breast cancer is heterogeneous, and diverse approaches are required to address its different manifestations, Yee says.

Yee and his colleagues are now developing an arm of the study called I-SPY2 Plus, which will allow doctors to switch drugs if a patient isn’t responding favorably to her assigned treatment.

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