First Prospective Trial Shows Molecular Profiling Timely for Tailoring Therapy

A clinical trial has shown that patients, and their physicians, are eager to jump into next-era cancer care — analysis of an individual’s tumor to find and target genetic mutations that drive the cancer. Results of the study, CUSTOM, are being presented at the 2013 annual meeting of the American Society of Clinical Oncology years before investigators thought they would be ready.

May 16, 2013

Patients were willing to undergo additional cancer biopsy to seek out best treatment for their tumor type.

(Washington, D.C.) – A clinical trial has shown that patients, and their physicians, are eager to jump into next-era cancer care — analysis of an individual’s tumor to find and target genetic mutations that drive the cancer. Results of the study, CUSTOM, are being presented at the 2013 annual meeting of the American Society of Clinical Oncology years before investigators thought they would be ready.

CUSTOM is the first completed prospective clinical trial that used genetic analysis alone to assign cancer treatment for patients with one of three different cancers.

"We expected it would take five years to enroll 600 patients into CUSTOM. But in less than two years, 668 patients were recruited," says the study’s lead investigator, Giuseppe Giaccone, MD, PhD, associate director for clinical research at Georgetown Lombardi Comprehensive Cancer Center.

"This was a surprise to all of us, especially since patients with advanced cancer who already had biopsies needed to undergo an additional biopsy for the study. But we found patients and their doctors are quite interested in this type of personalized medicine. They know that the molecular profile of the tumor is important," says Giaconne, who is also director of clinical research for the MedStar Georgetown Cancer Network, a regional oncology affiliation between MedStar Health and Georgetown Lombardi.

CUSTOM has proved to be a model for more efficient clinical trials, he adds. It showed that patients want to participate in this kind of research, and that it is feasible to do extensive genetic testing on a tumor biopsy in a timely manner — in this case, taking only two weeks to complete. It also demonstrated that it is safe to take new biopsy from patients with advanced cancer to provide the tissue needed for the analysis.

One of the other endpoints of the study, however, was not achieved. Researchers discovered that, in many cases, they did not have enough patients with rare cancer mutations to provide an accurate statistical analysis of response to novel drugs, says Giaccone.

Giaccone led the clinical trial while at the National Cancer Institute where he was the Chief of the Medical Oncology Branch, before he joined Georgetown in January. Researchers at Oregon Health & Science University also participated.

CUSTOM enrolled patients diagnosed with advanced stage non-small cell lung cancer, small cell lung cancer or thymic cancer. Researchers used next-generation sequencing, which was novel at the time, to look at almost 200 genes. From this, patients were assigned to different treatment groups based on genetic mutations or amplification.

Results from the largest group — patients with non-small cell lung cancer — had either an EGFR or a KRAS mutation, and results showed that those with EGFR mutations had a very high response to the drug erlotinib. "This is nothing new; we essentially confirmed what was already known," Giaccone says. But they also discovered that patients with KRAS mutations did not benefit from the single agent investigational drug selumetinib, which is being studied for use in a number of cancers, including non-small cell lung cancer.

Results for the patients with small cell lung or thymic cancers were inconclusive, primarily because the investigated mutations were rare —not enough patients had specific mutations to adequately test response to therapy. "When we started the study, we didn’t know how frequently the mutations occurred," Giaccone says. "Now we know that many mutations represent only 1 to 2 percent of patients and to do this right, you need to screen thousands of patients. That is only possible with a global study that involves, potentially, hundreds of institutions.

"The CUSTOM trial demonstrates both the feasibility of the approach for common mutations — that it is possible to have a real-time genetic analysis that guides treatment — as well as the difficulty of studying treatment for rare mutations," he says.

The Intramural Program of the National Cancer Institute funded the study. Giaccone reports having no personal financial interests related to the study.

About MedStar Georgetown University Hospital

MedStar Georgetown University Hospital is a not-for-profit, acute-care teaching and research hospital with 609 beds located in Northwest Washington, D.C. Founded in the Jesuit principle of cura personalis—caring for the whole person—MedStar Georgetown is committed to offering a variety of innovative diagnostic and treatment options within a trusting and compassionate environment.

MedStar Georgetown’s centers of excellence include neurosciences, transplant, cancer and gastroenterology. Along with Magnet® nurses, internationally recognized physicians, advanced research and cutting-edge technologies, MedStar Georgetown’s healthcare professionals have a reputation for medical excellence and leadership. MedStar Georgetown University Hospital—Knowledge and Compassion Focused on You.

About MedStar Health

MedStar Health combines the best aspects of academic medicine, research and innovation with a complete spectrum of clinical services to advance patient care. As the largest healthcare provider in Maryland and the Washington, D.C., region, MedStar’s 10 hospitals, the MedStar Health Research Institute and a comprehensive scope of health-related organizations are recognized regionally and nationally for excellence in medical care. MedStar has one of the largest graduate medical education programs in the country, training more than 1,100 medical residents annually, and is the medical education and clinical partner of Georgetown University. MedStar Health is a $4.5 billion not-for-profit, regional healthcare system based in Columbia, Maryland, and one of the largest employers in the region. Its almost 30,000 associates and 6,000 affiliated physicians all support MedStar Health’s Patient First philosophy that combines care, compassion and clinical excellence with an emphasis on customer service.

About Georgetown Lombardi Comprehensive Cancer Center

Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, visit lombardi.georgetown.edu.

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis — or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health.

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