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Oncology Times Features I-SPY 2 Trial in 2016 SABCS Highlights

The 2016 San Antonio Breast Cancer Symposium may be wrapping up, but the coverage is not over. Here are new research findings from day 5 to keep on your radar.

Liquid biopsy might not be a reliable surrogate for tumor biopsy in metastatic breast cancer

Liquid biopsy is a minimally invasive technique that holds immense potential for making treatment decisions in oncology, but the results of abstract P6-07-03 suggest a note of caution. The small study reports that circulating tumor DNA (ctDNA) in plasma, or a liquid biopsy, does not accurately reflect tumor DNA for metastatic breast cancer patients.

The researchers obtained blood samples and tumor samples from 7 patients with multiple advanced breast cancer lesions. Then they extracted and sequenced the DNA from the plasma, buffy coat, and tumor samples to identify mutations. The buffy coat served as the control.

Many mutations were found in the plasma DNA that could not also be found in the tumor DNA, suggesting plasma DNA does not comprehensively represent tumor DNA. The researchers cautioned that liquid biopsies might not be able to serve as a surrogate for tumor biopsy in metastatic breast cancer.

Immunotherapy pembrolizumab offers long-lasting response for metastatic triple-negative breast cancer

Earlier this year, KEYNOTE-012 reported encouraging results for pembrolizumab, a programmed cell death protein 1 (PD-L1) inhibitor, as an immunotherapy for patients with metastatic triple-negative breast cancer (mTNBC). The latest findings, as reported in Abstract P6-10-03, show that pembrolizumab can also provide long-lasting responses.

The phase Ib KEYNOTE-012 trial enrolled 32 women with mTNBC who were heavily pretreated and had PD-L1-positive tumors. The participants then received pembrolizumab for 24 months.

Five participants responded (one complete response [CR] and four partial responses [PRs]), and three of which have had long-lasting response. One stopped taking pembrolizumab 11 months after reaching CR and has maintained response for about 15 months. The other two had PRs and stayed on pembrolizumab for 2 years. Of these two, one maintained response for 22.7 months and the other for 7.7 months.

These results support further study of pembrolizumab for heavily pretreated patients with mTNBC.

I-SPY 2 trial reports results for two investigational drug studies

The I-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) uses an innovative design to predict the likelihood of a new treatment's success in a phase III trial. Overall, the I-SPY 2 trial evaluates whether adding an investigational drug to the standard neoadjuvant therapy is superior to standard neoadjuvant therapy. The latest findings for two investigational drugs are reported in two abstracts.

In Abstract P6-11-02, researchers reported the results for ganetespib, a heat shock protein 90 (Hsp90) inhibitor, for patients with high-risk stage II or III breast cancer. The aim was to determine whether adding ganetespib to standard neoadjuvant therapy led to better outcomes for this population of patients.

The researchers assigned 93 patients to receive ganetespib in addition to paclitaxel and 140 to receive paclitaxel alone. The study evaluated three of 10 pre-defined biomarker signatures. The three signatures were HER2 negative, hormone receptor (HR) positive/HER2 negative, and HR negative/HER2 negative.

For any new treatment to graduate from I-SPY 2, it must have at least an 85 percent Bayesian predictive probability of success in a 300-patient phase III neoadjuvant trial for one biomarker signature.

Ganetespib failed to reach 85 percent likelihood of success for all three signatures, but one signature, HR negative/HER2 negative, did come close at 72 percent and also had a 16 percent improvement in pathological complete response rate. The researchers did not recommend moving ganetespib to a phase III trial but did think combinations with ganetespib for neoadjuvant treatment could be worth pursuing.

In abstract P6-11-04, researchers reported results for ganitumab, a type 1 insulin-like growth factor receptor (IGF1R), as a neoadjuvant therapy for patients with high-risk stage II or III breast cancer. Because ganitumab can cause insulin resistance, patients who received ganitumab also received metformin, which treats type 2 diabetes.

The study enrolled 106 patients to receive ganitumab with metformin plus standard neoadjuvant chemotherapy and 128 to receive standard neoadjuvant chemotherapy. Standard neoadjuvant chemotherapy was paclitaxel plus doxorubicin and cyclophosphamide. The three biomarker signatures used were HER2 negative, HR positive/HER2 negative, and HR negative/HER2 negative.

For all three signatures, ganitumab failed to achieve 85 percent likelihood of success in a phase III trial. These findings do not support further study of this drug for neoadjuvant treatment of breast cancer.