The I-SPY 1 TRIAL

Designed to be a national resource, the I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis or I-SPY 1) is a collaboration between the National Cancer Institute and ten cancer centers across the country.

Benefits of a Neoadjuvant Setting

I-SPY 1 TRIAL involved serial imaging and bio-specimen collection for women with tumors at least 3 cm in size who underwent neoadjuvant therapy. Neoadjuvant therapy is chemotherapy given prior to surgery. Neoadjuvant therapy has the advantage of allowing us to actually see the tumor’s response to treatment before we remove it, and thus is the ideal platform to identify mechanisms of resistance, develop diagnostic indicators, and individualize therapy. Traditional drug development processes utilize adjuvant trials and require long follow-up, many thousands of patients, and may take ten to twenty years to go from laboratory bench to patient bedside. Moreover, substantial investment in time and resources is also required to identify drugs that will fail. In contrast, the neoadjuvant setting provides a forum to rapidly design and test new treatments.

Study Objective

The main objective of the I-SPY 1 TRIAL was to identify indicators of response to neoadjuvant chemotherapy that predict survival in women with high-risk (Stage II-III) breast cancer. For example, one goal was to determine if there was a correlation between a Magnetic Resonance Imaging (MRI) depiction of a tumor decreasing in volume after administering neoadjuvant chemotherapy and long-term survival/recurrence. A total of 237 participants were enrolled over a four-year period ending in March 2006. We extended the protocol to enroll an additional 119 participants in December 2010.

Certain principles were agreed upon at the onset of the trial:

• To share the data and bio-specimens with a goal of releasing this data for use by other researchers following the completion of the trial
• To adhere to data standards wherever they exist so that comparisons across platforms or with other trials would be possible
• To monitor the quality of the samples enabling the investigators to prospectively interpret the data.

These principles allowed us to have investigators and academic cancer centers across the country engage in the very important work of rapidly translating tissue and imaging markers/indicators into improved clinical care.

Conclusions

Breast cancer tumor profiles predicted the response of the tumors to chemotherapy drugs.

• One subset of participants fared well regardless of the chemotherapy they received. These participants are characterized as having a good prognosis.
• For the other participants, characterized as having a poor prognosis, it was determined that the tumor’s response to the neoadjuvant chemotherapy was a very good predictor of long-term, disease-free survival.
• The change in size of the tumor during treatment, as measured by an MRI, is a good predictor of the ultimate response to the treatment.

Investigators also found that most locally advanced breast cancers are discovered in the interval between routine mammogram exams, typically conducted every one or two years. Of the women participating in the trial who underwent regular screening mammograms, 83% were diagnosed with breast cancer outside their regular screenings. This finding suggests the effectiveness of early detection of locally advanced breast cancer by conventional screening is hindered by the fast growth rate of this type of breast cancer.

On the basis of these findings, the I-SPY 2 Team is now ready to take the next step - the I-SPY 2 TRIAL.