Professor Peter Schmid, Centre Lead for the Centre for Experimental Cancer Medicine, recently presented results from the OPPORTUNE clinical trial at the world's largest Breast Cancer meeting: the San Antonio Breast Cancer Symposium.
The results were presented on December 10th at the meeting, which is "designed to provide state-of-the-art information on the experimental biology, etiology, prevention, diagnosis, and therapy of breast cancer and premalignant breast disease, to an international audience of academic and private physicians and researchers" - around 7,500 delegates attended from almost 100 countries.
How was the trial set up?
OPPORTUNE is a window-of-opportunity (WOO) trial designed to find out whether a drug called Pictilisib (a PI3 kinase inhibitor) can help breast cancer patients. The question is: can Pictilisib enhance the anti-tumour effects of short-term, preoperative treatment with the aromatase inhibitor anastrozole (ANA) in ER-positive primary breast cancer?
The way the trial was designed means that our researchers had access to tumour tissue before and after treatment so that they could perform comprehensive biomarker analysis - checking the tumour samples for different proteins that represent tumour progression, plateaus or increases in growth - giving critical insight into the people who would most benefit from the treatment, as well as potential mechanisms of resistance to the drugs.
Earlier results have suggested that resistance to endocrine therapy approaches in breast cancer could rely on PI3K signalling pathways, so targeting them in addition to the standard therapeutic approach could help to avoid or delay resistance.
Professor Schmid said:
"Short-term preoperative WOO studies are a validated strategy for novel treatments to provide proof-of-concept and define the most appropriate patient population by directly assessing treatment effects in tumor tissue before and after treatment.”
Prof. Schmid and his colleagues recruited a total of 70 postmenopausal patients who were not receiving hormone replacement therapy and who had been newly diagnosed with operable ER+, HER2-negative breast cancer. They were then randomly assigned to receive 2 weeks of preoperative treatment with ANA + Pictilisib (44 patients, the "ANA+PIC" arm) or ANA alone (26 patients, the "ANA" arm),
What did the results show?
So far the data suggest that adding Pictilisib to the treatment regime could benefit patients with ER-positive, HER2-negative, early and operable breast cancers. Luminal B or highly proliferative tumors could also respond better to the new combination.
Prof. Schmid said:
“This first report of a preoperative window of opportunity study evaluating a PI3K inhibitor in early breast cancer demonstrated addition of pictilisib to ANA was associated with increased antiproliferative response over single-agent ANA.
“Mean post-treatment percentage reduction of Ki67* was 83.8 per cent for ANA+PIC and 66.0 per cent for ANA (P= 0.004) and 86 percent of ANA+PIC group patients responded compared with 53.9%% of those in the ANA-only group (P = -0.003).
Pictilisib did not increase tumor cell apoptosis over ANA alone but, importantly, the safety profile of the combination was “acceptable and consistent with other trials,” he added. *Ki67 is a marker of cell growth used to measure tumour cell growth and assess treatment effectiveness.
The presentation of the OPPORTUNE results was covered by Cancer Therapy Advisor.
Professor Peter Schmid, Centre Lead for the Centre for Experimental Cancer Medicine, recently presented results from the OPPORTUNE clinical trial at the world's largest Breast Cancer meeting: the San Antonio Breast Cancer Symposium...