FDA-cleared genomic profiling tests to guide cancer treatment

FDA-cleared genomic profiling tests to guide cancer treatment

Last Updated on December 27, 2017 by Joseph Gut – thasso

December 25, 2017 – The American Food & Drug Administration (FDA) has approved two genetic tests to identify genetic alterations in tumors.  The FoundationOne CDx (F1CDx) genomic test and the MSK-IMPACT Tumor Profiling test both can help to guide physicians in clinical trial enrollment and in cancer treatment.

The FoundationOne CDx (F1CDx) genomic test can identify cancer-associated alterations in 324 genes and two types of genomic signatures in any type of solid tumor, irrespective of the tissue the tumor initially originated from. Moreover, F1CDx can 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.

A couple of days before the F1CDx, FDA had cleared the MSK-IMPACT Tumor Profiling Test. This test. which was 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.

This latter test was at the base of research using the concept of a basket clinical study, which harnessed the power of precision medicine by assigning treatments to patients based on the genetic alterations and led to the recent approval of Vemurafenib (Zelboraf) for the treatment  of BRAF V600E positive Erdheim-Chester Disease (ECD) based on the data of 22 ECD patients enrolled in the phase II VE-BASKET study.

Of note in this context is that 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. Still, CMS’ coverage proposal, known as a national coverage determination, is subject to a 30-day public comment period before it can be finalized.

Tumor profiling tests are increasingly influencing patient care. The F1CDx test is the second commercial next-generation sequencing-based test for cancer to be approved by FDA after the Oncomine Dx Target Test, the first in its class in June 2017. However, F1CDx is the first next-generation sequencing test for cancer to be reviewed as part of an FDA/CMS initiative designed to speed promising new technologies to market. By using this parallel review program FDA is able to bring patients faster access to a breakthrough diagnostic that can help doctors tailor cancer and/or other treatments to improve medical outcomes and potentially reduce health care costs., 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.

Under the newly emerging concept of “One Clinical Trial, Many Cancer Types” clinical trials in cancer (also coined “basket 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).  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 do really add up to significant subsets of patients, and it would never be cost-effective to screen for these alterations one at a time.

Judge here for yourself the power of these new tests and the amount of actionable knowledge towards clinical therapy decisions generated by following  the impressive list of 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 (Mekinist®) or Cobimetinib (Cotellic®) in combination with Vemurafenib (Zelboraf®)
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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Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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