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Genomic Profiling Tests Cleared by FDA Can Help Guide Cancer Treatment, Clinical Trial Enrollment

, by NCI Staff

Credit: Caroline Davis2010. CC BY 2.0

Over the past month, the Food and Drug Administration (FDA) has approved two tests to identify genetic alterations in tumors.

The most recent approval, on December 1, is the FoundationOne CDx (F1CDx) genomic test, which can identify cancer-associated alterations in 324 genes and two types of genomic alterations—called genomic signatures—in any type of solid tumor.

Among other uses, the approval allows F1CDx to be used as a companion diagnostic test for 15 different targeted therapies used to treat five types of cancer (see table at bottom). A companion diagnostic is used to determine whether a patient is a candidate for a specific therapy by identifying whether their tumor has a specific genetic alteration.

Data that led to the test’s approval showed that it could accurately detect selected mutation types about 95% of the time.

On the same day, the Centers for Medicare & Medicaid Services (CMS) proposed national coverage of F1CDx and certain other diagnostic tests that use next-generation sequencing technology, which can rapidly analyze many genes simultaneously.

The proposed coverage includes the use of these tests in patients with recurrent or metastatic solid cancers who have not previously used the test and who wish to pursue further treatment for which the test can serve as a companion diagnostic.

CMS’ coverage proposal, known as a national coverage determination, is subject to a 30-day public comment period before it can be finalized.

MSK-IMPACT Tumor Profiling Test Cleared

FDA’s approval of F1CDx follows closely on the heels of its November 15 authorization of another next-generation sequencing test to analyze genetic changes in patients’ tumors.

That test—called MSK-IMPACT and developed for use only at Memorial Sloan Kettering Cancer Center (MSKCC) in New York—can scan tumor samples for 468 different cancer-associated mutations or alterations.

Laboratory tests developed by and used only at a single hospital currently do not require FDA review and authorization to be offered to patients.

But as tumor profiling tests are increasingly influencing patient care, having a process in place for institutions to show that these tests meet standards for quality and reliability is important, said Tracy Lively, Ph.D., chief of the Diagnostics Evaluation Branch in NCI’s Division of Cancer Treatment and Diagnosis.

“I’m very pleased to see that we’re now getting an FDA label on tests like these, which are very broad panels not tied to any specific tumor type or specific drug,” added Dr. Lively.

“Both tests enable physicians to look at a broad range of genetic abnormalities in their patients’ tumors, some of which might be tied to particular approved drugs and some of which might be useful for other reasons,” such as identifying potential participants for clinical trials, she continued.

A major advantage of multigene tests is their ability to get a lot of information out of a single tissue sample, explained Dr. Lively. This is important because it can often be difficult to get enough tissue from a tumor biopsy for several separate tests.

New Review Pathways for Genomic Tests

The F1CDx test is the fifth next-generation sequencing-based test for cancer to be approved by FDA, but is the first such test to be reviewed as part of an FDA–CMS initiative designed to speed promising new technologies to market.

By using this parallel review program, “we’ve been able to bring patients faster access to a breakthrough diagnostic that can help doctors tailor cancer treatments to improve medical outcomes and potentially reduce health care costs,” said FDA Commissioner Scott Gottlieb, M.D., in a press release.

Along with the MSK-IMPACT authorization in November, FDA also announced a new, streamlined regulatory process that hospitals and medical institutions can use to secure FDA authorization for their own in-house tumor profiling tests without having to go directly through the agency, which can be expensive and time consuming.

Dr. Lively said that many institutions may still not have the resources to seek approval for their in-house developed genomic tests and may not want to switch to a commercial test like the F1CDx.

“Neither situation should reflect negatively on those institutions or their tests,” many of which have been developed for specific types of cancer or to look for certain genetic mutations under study at a research center, she explained.

One Clinical Trial, Many Cancer Types

Cancer clinical trials are increasingly enrolling patients based not on the organ in which a tumor initially arose—such as the breast, colon, lung, or liver—but on the specific genetic alterations that allow the tumor to survive and spread. These targets can include mutations in single genes or genomic signatures such as microsatellite instability or mutation burden (the number of mutations in a single tumor).

These “basket trials,” as they’re called, are “a new concept that a broad [genetic] test greatly facilitates,” said David Klimstra, M.D., chair of the pathology department at MSKCC.

“Our clinical trial enrollment at MSKCC has been on a rapid upswing since MSK-IMPACT was launched,” he added.

Research published earlier this year showed that MSK-IMPACT identified actionable genetic changes in 37% of patients with advanced solid cancers. An actionable mutation is one that can be targeted with either an approved drug or one being tested in clinical trials.

Taken together, patients with a variety of rare but actionable mutations “really add up to a significant subset,” said Marc Ladanyi, M.D., chief of molecular diagnostics at MSKCC.

“It would never be cost-effective to screen for these alterations one at a time, but using a panel makes the whole proposition work,” Dr. Ladanyi continued. “We’re able to identify these patients and get them into trials, most of which have been quite successful at showing improved outcomes.”

Cancer types for which F1CDx can serve as a companion diagnostic
Cancer Type Gene Containing Targeted Mutations Drug
Non-small cell lung cancer EGFR Erlotinib (Tarceva®), afatinib (Gilotrif®), or gefitinib (Iressa®)
Non-small cell lung cancer EGFR Osimertinib (Tagrisso®)
Non-small cell lung cancer ALK Crizotinib (Xalkori®), alectinib (Alecensa®) or ceritinib (Zykadia®)
Non-small cell lung cancer BRAF Dabrafenib (Tafinlar®) in combination with trametinib (Mekinist®)
Melanoma BRAF Vemurafenib (Zelboraf®) or dabrafenib
Melanoma BRAF Trametinib or cobimetinib (Cotellic®) in combination with vemurafenib
Breast cancer HER2 (ERBB2) Trastuzumab (Herceptin®, Ogivri™), pertuzumab (Perjeta®) or ado-trastuzumab emtansine (Kadcyla®)
Colorectal cancer KRAS Cetuximab (Erbitux®)
Colorectal cancer KRAS, NRAS Panitumumab (Vectibix®)
Ovarian cancer BRCA1, BRCA2 Rucaparib (Rubraca®)
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