Most Efficient, Less Costly Gene Testing Method for NSCLC

Roxanne Nelson, BSN, RN

May 17, 2018

UPDATED May 21, 2018 // Genetic testing is now the standard of care for all patients with metastatic non–small cell lung cancer (NSCLC) for identifying patients who could benefit from targeted therapy. Genetic testing was originally used to test for individual genes. It now involves next-generation sequencing (NGS), which identifies many genes. A new study suggests that this may be the optimal method.

The study, which employed a model that used hypothetical patients and cases, compared NGS with single-gene testing and sequential testing.

Using NGS up front "resulted in the fastest turnaround time and the highest percentage of patient with targetable alterations identified and the lowest cost all around," said lead author Nathan A. Pennell, MD, PhD, codirector of the Cleveland Clinic Lung Cancer Program in Ohio.

In addition, the model estimates that NGS could save as much as $2.1 million for Medicare and more than $250,000 for commercial insurance providers.

Pennell spoke at a press briefing held ahead of the American Society of Clinical Oncology (ASCO) 2018 annual meeting, where the new study will be presented on June 3 (abstract 9031).

The authors acknowledge that a limitation of their study is that they made several assumptions in developing model. Going forward, they would like to evaluate actual health systems and test cost-efficiency in a real-world setting.

Lowest Cost, Fastest Results

At the press briefing, Pennell explained that a growing number of genes are known to be altered in NSCLC, including EGFR, ALK, ROS1, BRAF, MET, HER2, RET, and NTRK1. So far, four of these (EGFR, ALK, ROS1, and BRAF) can be targeted with therapies that have been approved by the US Food and Drug Administration (FDA). Investigational agents that target other alterations are currently being evaluated in clinical trials.

A number of tests are currently available for genetic testing, but there is no accepted standard as to when and how the testing should be performed, he explained.

For the study, Pennell and colleagues developed a decision analytic model using Center for Medicare & Medicaid Services (CMS) and commercial health plans with 1 million hypothetical members. They drew on data from both the CMS and commercial health plans to estimate costs for each modality.

The model involved 2221 patients with newly diagnosed NSCLC. It was assumed that the patients would receive testing for PD-L1 and genomic alterations (EGFR, ALK, ROS1, BRAF, MET, HER2, RET, NTRK1), using one of the following testing methods: sequential tests; exclusionary mutation (KRAS) test followed by sequential tests; panel test; or up-front NGS that included all genomic alterations and KRAS.

Those assigned to the first three cohorts were also tested for genomic alterations that can be targeted with approved therapies (EGFR, ALK, ROS1, BRAF) and with single-gene tests or NGS for other mutations, such as HER2.

"We also assumed that a certain percentage would want to go on and be tested for other genes and a certain percentage would exhaust the biopsy tissue and need a rebiopsy," he said.

The estimated time to receive results from NGS was 2 weeks, which was 2.7 weeks faster than results were available for the exclusionary group and 2.8 weeks faster than sequential testing.

For CMS reimbursement, NGS yielded a savings of $1,393,678 compared with exclusionary testing, $1,530,869 compared with sequential, and $2,140,795 compared with panel testing. Among patients covered by commercial payers, NGS was also the least expensive option: $3809 compared with exclusionary testing, 127,402 compared with sequential testing, and $250,842 compared with panel testing.

Commenting on the study, ASCO President Bruce E. Johnson, MD, FASCO, who is also chief clinical research officer and institute physician at the Dana-Farber Cancer Institute in Boston, Massachusetts, noted that although only four agents are currently available that target specific genetic alterations, two to four drugs may soon become available.

"It becomes a real challenge to have to go back and resequence patients," he said.

NGS panels can sequence between 50 and 400 genes, "so this is welcome news to those who are ordering these gene panels," Johnson pointed out. "You get a lot more information, and at a cost that is competitive or less."

Also commenting on the study, ASCO Chief Medical Officer Ricard Schilsky, MD, told Medscape Medical News, "It's important to note that this is a hypothetical study — these are not real data from real patients from real medical records, so there's a lot of assumptions being made that are reasonable but may not necessarily be correct."

In addition to the four gene alterations for which there are FDA-approved therapies, there are "also a bunch of other mutations that could navigate a patient to an off-label use of an FDA-approved therapy, for instance, HER2 mutations and treatment with trastuzumab," he noted.

In addition, NGS testing gives broader information, Shilsky noted. For example, both a single gene test and an NGS test would indicate the same EGFR mutation, which would suggest use of an EGFR drug, but the NGS test would also reveal a KRAS mutation, which would be a contraindication to the EGFR therapy because KRAS is associated with resistance to those drugs. "Or you may learn about other mutations which you may not act on immediately but which may become useful after the patient has progressed on first-line therapy, and it could inform second-line therapy," he added.

"This is an example where technology is proceeding more quickly than the evidence of clinical utility to support actually using the technology," Schilsky told Medscape Medical News.

"But that evidence is coming on very quickly, and the fact that we now have an FDA-cleared and an FDA-approved NGS test, both of which are going to be approved by Medicare, indicates that this is clearly coming on into the mainstream," he added.

Commenting about this abstract on Twitter, Jack West, MD, from the Swedish Cancer Institute, in Seattle, Washington, said: "This is a model that ignores costs of treatment with ineffective therapies initiated by NGS. It's not actual data, and it smacks of being heavily promoted by all vested interests who benefit from marketing NGS. Not a data release as much as a lobbying/marketing campaign."

The study received funding from Novartis. Dr Pennell has had a consulting or advisory role with AstraZeneca, Lilly, and Regeneron and has received research funding (institutional) from Genentech, Newlink Genetics, Clovis Oncology, Astex Pharmaceuticals, Celgene, AstraZeneca, Pfizer, and Merck. Other coauthors have also disclosed relationships with industry.

American Society of Clinical Oncology (ASCO) 2018. Abstract 9031, to be presented June 3, 2018.

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