A first-of-its-kind, large scale trial of whole genome cancer testing to personalize treatment for patients with metastatic breast cancer finds in 20 percent of the cases uncovered rare and unexpected genomic activity and argues it’s time to make this approach a clinical standard.
A French research consortium presented the findings from their study at the 2012 European Society for Medical Oncology Congress in Vienna. The results were based on biopsies performed in 402 breast cancer patients, including 26 patients for whom analyses are ongoing.
Of those patients, a genomic result could be generated in 276 patients, including whole genome analysis in 248. A genomic alteration “targetable” by an anticancer drug was found in 172 of those patients. About 20 percent of the patients presented a very rare and sometimes unexpected genomic alteration, highlighting the need for whole genome approaches, the researchers said.
The researchers sequenced the entire genome from a biopsy of a metastatic lesion that was analyzed prospectively for individual patients with metastatic breast cancer. They identified the genetic alterations in the metastatic tissue, which allowed them to identify which genes were mutated, amplified or deleted. The researchers proposed different targeted therapies based on their findings.
“The main message is that whole genome approaches can be delivered in the context of daily practice in large cohorts, allowing us to identify targets that can be inhibited in a high proportion of patients, leading to anti-tumor effects,” says Fabrice André from Institute Gustave Roussy. “This study suggests that time has come to bring personalized medicine to the cancer field.”
He says that the theoretical benefit of whole genome testing is that this approach can identify both frequent and rare unexpected genomic events. “In addition, it allows us to quantify the level of genomic instability, and to detect whether driver mutations are associated with genomic alterations involved in resistance to targeted agents,” he says.
Although only a minority of patients needed an investigational agent since the biopsy, 26 patients so far received a targeted agent matched to the genomic alteration. The goal is to reach more than 80 patients treated with a targeted agent. When results from the trial and its pilot phase are pooled, 18 out of 48 patients treated according to whole genome analysis presented evidence of antitumor activity, André says.
“In the future, we think that whole-genome approaches to genomic testing of cancer will be the standard of care since they provide a broad picture of genomic alterations and an easy way to test biomarkers,” he says. Peter Dubsky, associate professor of surgery at the Medical University of Vienna, who was not involved in the study, said it was a “remarkable accomplishment that has moved personalized molecular dissection of breast cancer into a setting that is, in principle, transferable into clinical practice.”
“The French consortium has opened a new door to more personalized treatment of advanced breast cancer,” Dubsky says. “Clinical research will have to address the clinical utility of such approaches compared to current standards.”
He notes that the definition of breast cancer subtypes is already a clinical reality in the treatment of advanced and early disease. Whole genome approaches, he says, will have to be compared to this current gold standard in terms of their clinical utility.
October 05, 2012
http://www.burrillreport.com/article-breast_cancer_study_points_to_personalized_treatments.html