Two large clinical trials are expected to define the impact that employing genomic tests in treatment decisions has on survival outcomes, according to Martine J. Piccart, MD, PhD.
Martine J. Piccart, MD, PhD
Although multigene signature tests are being widely used in the United States to help oncologists evaluate the need for adjuvant chemotherapy for certain patient populations, two large clinical trials are expected to define the impact that employing genomic tests in treatment decisions has on survival outcomes, according to Martine J. Piccart, MD, PhD.
Piccart, director of Medicine at the Jules Bordet Institute in Brussels, Belgium, discussed genomic testing and its translational value thus far during a presentation and subsequent interview Friday morning at MBCC.
As president of the European Society of Medical Oncology, Piccart recently cautioned that the era of personalized medicine has not truly arrived, and she echoed that theme in her remarks at the conference.
She said that although “we have witnessed the development of several quite good multigene prognostic signatures,” not much progress has been made in terms of predictive tools that help clinicians select the best chemotherapy.
“We’ve come to realize that identifying predictive markers is really a very complex endeavor,” Piccart said. “One of the reasons that we have probably failed up until now is that we have concentrated our efforts on the tumor and it’s becoming incr easingly [apparent] that the macroenvironment plays a major role.”
In less than a decade, prognostic genomic testing has become widespread in the United States, but less so in Europe, Piccart noted. “Information generated from genomic tests has resulted in a change in decision making in approximately 25% to 30% of cases,” according to the IMPAKT 2012 Working Group, a cooperative translational research effort in Europe that Piccart helped develop.1
Last year, IMPAKT researchers evaluated six genomic tests for their analytical validity, clinical validity, and clinical utility.1
The researchers concluded that OncotypeDX, a 21- gene recurrence score, and MammaPrint, a 70-gene assay, have demonstrated analytical and clinical validity.
OncotypeDX has been incorporated into the American Society of Clinical Oncology and N ational Comprehensive Cancer Network guidelines; it is indicated for women with stage I/II, node-negative, estrogen receptor- positive invasive breast cancer who will be tr eated with hormone therapy and provides a score for the risk of local recurrence.
The IMPAKT group said there are not enough available data to arrive at a conclusion on t he analytic and clinical validity of four other tests: CGI, a 97-gene assay; PAM50, a 50-gene assay; the Breast Cancer Index, a 2-gene ratio and molecular grade index; and EndoPredict, an 11-gene assay.
Piccart said EndoPredict has been gaining popularity in Europe. She said that EndoPredict incorporates information on Ki67, a nuclear antigen used to compare proliferation between tumor samples2, and on tumor burden to predict for long-term disease-free survival.
So far, the genomic tests have aided in treatment decisions, Piccart said. She said the tests are useful for luminal breast cancers, not for HER2-positive or triple-negative malignancies that would automatically be classified as high risk.
“These tests are already now quite useful in the clinic and have already led to a significant decrease in adjuvant chemotherapy prescription in the United States,” Piccart said in an interview.
“We are still waiting for the results of these very important trials, TAILORx and MINDACT, to be completely sure that these tests are clinically useful and improve the outcome of patients,” she said. “In this case, what we expect is a reduction in chemotherapy prescriptions without any worsening of survival.”
TAILORx, which involves about 11,000 women, is comparing the disease-free survival of women with previously resected axillary-node negative breast cancer with an Oncotype DX Recurrence Score of 11 to 25 treated with adjuvant combination chemotherapy and hormonal therapy versus adjuvant hormonal therapy alone.3
MINDACT, which involves 6600 women, compares the 70-gene signature with standard clinical-pathological criteria used to determine whether patients with breast cancer with 0 to 3 positive nodes should receive adjuvant chemotherapy.4