Genomic analysis yields abnormalities associated with targeted treatments in rare and poor prognosis cancers

Analyzing tumors through clinical grade Next Generation Sequencing (NGS) technology has been useful in identifying genetic abnormalities in tumors that may make them vulnerable to molecularly targeted cancer treatment. Genomic analysis typically is conducted on more common cancers like breast and prostate, for which numerous therapy options already exist. Through the precision medicine initiative at the Cancer Institute, a clinical trial examined tumors of patients with rare or poor prognosis cancers.

Tissue specimens from 92 patients were analyzed using Foundation Medicine's FoundationOne™ platform for targeted sequencing of the entire coding sequence of 236 genes. While a majority of cases were deemed rare or uncommon, there were cases of advanced colon cancer and triple negative breast cancer enrolled that were either recurrent or non-responsive to standard treatment.

In 93 percent of the cases, at least one genomic alteration was found. The average number of alterations identified was 3.6. The majority of cases had mutations for which there were targeted therapies or clinical trials potentially available as assessed by a panel of clinicians, scientists, statisticians, pathologists and other experts at the Cancer Institute, collectively known as a molecular tumor board. Along with their genomic profile, a clinical case history of each patient was reviewed as part of the overall assessment. As appropriate, either potential enrollment in a clinical trial, treatment with already-approved cancer therapies or treatment with therapies approved for other uses were considered.

"Targeting a specific abnormality in a patient's cancer instead of just the organ where the cancer was first identified provides opportunities to personalize treatment regimens," notes lead author Kim M. Hirshfield, MD, PhD, medical oncologist at the Cancer Institute and assistant professor of medicine at Rutgers Robert Wood Johnson Medical School. "Sequencing results led to novel clinical action being implemented in a subset of these cases. Given that the standard of care typically is not effective in treating rare and poor prognosis cancers, these results are quite encouraging."

Advances in sequencing technology enable clinical results to be delivered in weeks, compared to the months required for in-depth sequencing on prior platforms. Such rapid delivery is key says senior author Shridar Ganesan, MD, PhD, associate director for translational science at the Cancer Institute and associate professor of medicine and pharmacology at Robert Wood Johnson Medical School. "Coupled with the knowledge and expertise of an institutional molecular tumor board, this rapid technological response enables investigators to begin to put theory into practice almost immediately. By drilling down and examining potentially actionable genomic features we can better identify tailored treatment strategies and strive to obtain better outcomes for our patients," he says.

"Genomic analysis allows us to go beyond a 'one size fits all' approach for treatment," notes Lorna Rodriguez, MD, PhD, director of the precision medicine initiative at the Cancer Institute and professor of obstetrics, gynecology and reproductive sciences at Robert Wood Johnson Medical School. "Not only do such findings help guide the use of existing therapies, but they also help in the development of future treatments in the form of new clinical trials."