First large scale trial of whole-genome cancer testing for clinical decision-making reported

Public release date: 1-Oct-2012 [ | E-mail | Share ]

Contact: ESMO PRESS OFFICE media@esmo.org European Society for Medical Oncology

VIENNA, Austria, 1 October 2012 For the first time, researchers have conducted a large trial in which they tested the entire genome of individual breast cancers to help personalize treatment. They released their findings at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.

In recent years, a number of drugs have been developed that target specific genetic alterations in cancer. To choose which of these drugs are suitable for individual patients, some genetic testing is performed. "In most of these cases, these genetic testing approaches only analyze a limited number of genes," said study author Dr Fabrice Andr from Institute Gustave Roussy, Villejuif, France.

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," Dr Andr said.

In terms of healthcare delivery and policy, developing whole-genome approaches also means new bioassays do not need to be designed for each new target discovered in cancer.

In the SAFIR01 trial, Dr Andr and colleagues developed a program where the entire genome from a biopsy of a metastatic lesion was analyzed prospectively for individual patients with metastatic breast cancer. They used array CGH (aCGH) and Sanger sequencing to identify the genetic alterations in the metastatic tissue, which allowed them to identify which genes were mutated, amplified or deleted. This genomic information was prospectively used to propose different targeted therapies. The study was conducted and sponsored by UNICANCER and funded by the French National Cancer Institute.

As of 23 September 2012, biopsies had been performed in 402 breast cancer patients, including 26 patients for whom analyses are ongoing. Of those, 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, Dr Andr said. Interestingly, around 20% of the patients presented a very rare and sometimes unexpected genomic alteration, highlighting the need for whole genome approaches.

"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. This study suggests that time has come to bring personalized medicine to the cancer field," Dr Andr said.

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.

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First large scale trial of whole-genome cancer testing for clinical decision-making reported