New Gene Test IDs Patients for Cancer Drug

Lung cancer patients with ALK gene mutation can be quickly identified with new test

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Targeted therapy can do wonders. The trick is finding which patients have the genetic mutation or some other alteration that drugs can effectively target.

Crizotinib (Xalkori) fights non-small cell lung cancer (NSCLC) tumors in patients whose cancer cells have a genetic alteration called ALK rearrangement.

A new test may be the answer to quickly find out if a patient is ALK-positive and will benefit from crizotinib.

"Ask a doctor about cancer gene mutation tests."

Chris M.J. Conklin, MD of the Department of Cellular and Physiological Sciences at the University of British Columbia, led the research. According to the American Cancer Society, 2 to 7 percent of non-small cell lung cancers have ALK (anaplastic lymphoma kinase) gene mutations, or rearrangements. Altered ALK enzymes trigger growth of certain NSCLC cells.

Crizotinib blocks the mutated ALK, which is an Achilles’ heel for some cancers. Studies have shown about 90 percent of patients with the ALK rearrangement have benefited from the medication.

Immunochemochemistry (IHC) is a process for detecting antigens (proteins) in cells of a tissue. Using this method, scientists stain a cancer tissue sample and can identify if a patient is ALK-positive according to the tissue reaction.

This research confirmed the use of IHC to identify the presence of ALK rearrangements.

The current standard method to detect ALK rearrangement is a test called FISH (fluorescence in situ hybridization). However, FISH is not readily available in most laboratories because it is time consuming and requires advanced technical and professional expertise.

Study authors say that IHC, in contrast, is relatively inexpensive, faster and is perfectly adapted for routine practice by academics and most community hospitals.

While prices vary, NYU Langone Medical Center lists the price for regular IHC at $10. Related other costs may add on another $10 to $25.

Researchers reviewed 377 stage I or II NSCLC cases. Tissue microarray results were available on 377 cases by IHC and 273 cases by FISH. A microarray indicates which genes are being expressed in any one tissue at any one time. Eleven cases were ALK-positive or possibly positive by either IHC or FISH, and three cases were positive or possibly positive by both methods.

Fred Hirsch, MD, professor of medicine and pathology and associate director of international programs at University of Colorado Cancer Center in Aurora, told dailyRx News, that studies in the EU and Japan have found similar results, which has led to the recommendation of ALK IHC as a screening tool for ALK gene rearrangement.

“I agree with the authors that ALK FISH is very skill-dependent and more costly than ALK-IHC,” said Dr. Hirsch. “However, it is important that IHC is performed under standardized conditions. In the US, the FDA approval for use of crizotinib is conditioned with the requirement that the molecular abnormality is demonstrated by an FDA-approved companion diagnostics and FISH is currently the only FDA-approved assay.

However, as a screening tool, ALK-IHC is a reliable tool to identify NSCLC patients with ALK gene rearrangement. Hopefully, in the future, the diagnostic paradigm will be defined to ensure that all the patients, who eventually could benefit from an ALK-inhibitor, will be captured.”

This study was published in the January 2013 issue of the International Association for the Study of Lung Cancer’s (IASLC) Journal of Thoracic Oncology.

Reviewed by: 
Review Date: 
December 18, 2012
Last Updated:
December 27, 2012