Test Shows Significance of Screening for Genomic Variants That Could Impact Treatment

To help reduce the chance of drug-induced toxicities and improve patient outcomes, NantOmics has developed a test that utilizes pharmacogenomic screening of patients to identify potential genomic variants that could impact treatment decisions. In results from the NantOmics pharmacogenomics test, which were presented at the 2018 AACR Annual Meeting in Chicago, Illinois, more than 7% of patients were determined to have a variant that could potentially alter the course of their treatment.

“Most patients (>95%) had at least 1 variant screened for in our pharmacogenomics panel. Of those, a surprising percentage had variants with the potential to change treatment due to severe or life-threatening implications,” the study authors wrote in their poster.

Pharmacogenomics is the study of the role of the genome in response to drug treatments, and combines pharmacology and genomics to help tailor treatments to a person’s specific genetic makeup. This is an important part of identifying patients who may or may not respond to a treatment, avoiding adverse events, and optimizing drug doses.

The NantOmics pharmacogenomics test used whole genome and whole exome sequencing of formalin fixed paraffin embedded tumor samples and matched normal samples from Clinical Laboratory Improvement Amendments (CLIA) patients. Both germline and somatic variants were tested to predict how a patient would respond to routinely-used treatments for cancer.

The clinical panel used in the test consisted of 30 biomarkers that are related to toxicities from 15 different therapeutics. For example, the CYP3A5*3, CYP3A5*6, and CYP3A5*7 alleles were related with tacrolimus treatment.

The frequency of such alleles was found with the pharmacogenomic panel, which corresponded closely with known population frequencies. The CYP3A5*3 allele is found in 85% to 95% in the population, which was similar to the frequency found in the study population of 84.43%.

Overall, 1123 patients (95.82%) had at least 1 pharmacogenomic variant that was found as a result of the test. These variants are common across many different cancer types. For example, 359 patients in the study population had a cancer of the gastrointestinal tract, and of these, 343 (95.5%) had at least 1 variant. All 56 patients with ovarian cancer had at least 1 variant, as did all 21 patients with bladder cancer.

Among the 1123 patients with a found variant, 86 (7.34%) had a variant that could potentially impact their treatment. Twenty-four patients (6.69%) with gastrointestinal tract cancer, 17 (7.94%) with breast cancer, 10 (10.75%) with bone or soft tissue sarcoma, and 8 (9.09%) with lung cancer had a variant that would be potentially impactful on their response to treatment. The frequency of each variant found among each cancer type was not presented in the poster.

The pharmacogenomic test used novel methods to examine more complex genotypes and structural variation. For example, the test studied genotypes that consist of more than 1 variant, such as the TPMT*3A allele that is made up of 2 single nucleotide polymorphisms, using RNA allele fractions. CYP2D6 is another gene that is complicated to genotype, and exon coverage was used to detect the copy number variants of this gene and its pseudogene CYP2D7.

A validation study was completed in a cohort of patients that were previously genotyped by a polymerase chain reaction—based panel that was independently validated by the CLIA and using cell lines from the Centers for Disease Control. This validation study showed that the test effectively detects each variant in the panel and correctly determines the patient genotype.

As a result of the pharmacogenomics test’s utility, the investigators noted that pharmacogenomic screening should be used more for patients undergoing cancer treatment. The study authors referenced FDA labels as an example, many drug labels contain pharmacologic warnings, and yet screening is not routinely done in patients to address these labels. Increased pharmacogenomic screening could help to identify patients with genotypes that impact their responses to particular cancer treatments.

Reference:

Schwartz C, Little J, Vaske C, et al. The NantOmics Pharmacogenomics Test: An integrative panomic approach to pharmacogenomics screening. Presented at: 2018 AACR Annual Meeting; April 14-18, 2018; Chicago, IL. Abstract 3888.