Routine, Targeted Next-Generation Sequencing Is Feasible for Patients with Non-Small Cell Lung Cancer

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Researchers retrospectively examined 2448 cases of NSCLC submitted to a single diagnostics lab over 3 years.
Researchers retrospectively examined 2448 cases of NSCLC submitted to a single diagnostics lab over 3 years.

Single-gene testing for driving mutations does not provide as much clinically relevant information as targeted next-generation sequencing (NGS) for patients with non-small cell lung cancer (NSCLC), according to research published in the Journal of Clinical Pathology.1

“NGS-based approaches permit testing at many sites within many genes, and thus have the advantage of being able to identify some of the rarer, but nonetheless actionable, mutations in EGFR, as well as alternative drivers, potential treatment modifiers, or prognostic indicators in EGFR mutation-negative tumors,” the researchers wrote.

To test the viability of using an NGS panel-based assay in routine practice, researchers retrospectively examined 2448 cases of NSCLC submitted to a single diagnostics lab over 3 years. The lab used Life Technologies' Oncomine Solid Tumor Panel to assess the mutations present in each patient sample.

The targeted panel assay detected a driver event in 65% of cases and, in 2017 specifically, the test identified either a driver event or tumor-specific variant in 83% of samples. Mutations in KRAS, EGFR, or another driver mutation were found in 35%, 17%, and 5.4% of samples, respectively, with an average turnaround time of 7 business days.

Importantly, they pointed out that if they had used the standard polymerase chain reaction (PCR)-based testing methods that evaluate only one gene, they would have either missed or incorrectly identified 12% of EGFR driver mutations and 21% of EGFR resistance mechanisms.

Though the current guidelines in the United Kingdom mandate the testing of only one gene in patients with NSCLC, the investigators estimated this technique yields a negative or uninformative result in nearly 80% of patients, while the use of at least a 22-gene panel reduces the chance of these types of results to 65%.

An author of the study, David Moore, MD, from the Department of Pathology at the UCL Cancer Institute in the United Kingdom, told Cancer Therapy Advisor that the 22-gene targeted NGS panel is mainly used by the United Kingdom state health care provider, The National Health Service, "as the cost in this sector is competitive with single-gene testing." However, he said the cost of single-gene testing can also vary depending on the method employed by the lab and the lab's turnaround time.

Not only can somatic variant analysis provide useful information about which patients would be good candidates for targeted therapies, it also provides key information about who is EGFR-negative, which the researchers argued could also inform physicians about novel driver mutations and help them decide who may be good candidates for treatment with alternative targeted therapies that are being investigated in clinical trials.

Based on their findings, the researchers concluded that in more established labs that process many samples (where cost of testing and turnaround time are less of a concern), it is viable to employ more in-depth sequencing than the current PCR-based testing methods that only evaluate one gene.

“A panel such as the one we have described, the costs of which is comparable to, or marginally more than a single-gene test, will identify the driver event in around two-thirds of cases (unlike a single EGFR test, which identifies the driver in around 15% of Western world lung cancer patients),” Dr Moore said. “As driver events are typically mutually exclusive, only the one-third of cases negative by our assay would be worthy of further testing using a more comprehensive gene panel covering many hundreds of genes and costing many times more. The same approach after single-gene testing would see 85% of lung cancer cases going on to have a very costly large scale gene panel test.”

Reference

  1. Moore DA, Balbi K, Ingham A, et al.  Analysis of a large cohort of non-small cell lung cancers submitted for somatic variant analysis demonstrates that targeted next-generation sequencing is fit for purpose as a molecular diagnostic assay in routine practice [published online July 27, 2018]. doi: 10.1136/jclinpath-2018-205319

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