National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
July 24, 2012 • Volume 9 / Number 15

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FDA Update

FDA Approves Test to Identify Colorectal Cancer Patients Who May Respond to Cetuximab

The Food and Drug Administration (FDA) has approved a genetic test to help physicians determine which patients with metastatic colorectal cancer are likely to benefit from the drug cetuximab (Erbitux).

The therascreen KRAS RGQ PCR Kit can detect seven mutations in the KRAS gene in DNA extracted from a patient’s tumor.

Activation of the epidermal growth factor receptor (EGFR), which is often overexpressed on the surface of colorectal cancer cells, promotes cell proliferation. The monoclonal antibody cetuximab binds to EGFR and blocks the receptor’s growth-promoting signaling pathway. Cancer cells that have a mutant KRAS gene, however, can continue to grow even in the presence of cetuximab.

FDA approval of the test was based on a retrospective analysis of biopsy samples from patients participating in the phase III CO.17 clinical trial that supported the original approval of cetuximab. Patients whose tumors lack KRAS mutations (also known as KRAS wild-type tumors) had an overall survival of 8.6 months with the addition of cetuximab compared with 5.0 months with best supportive care alone. For patients whose tumors had KRAS mutations, adding cetuximab did not significantly affect survival.

The FDA has also approved cetuximab in combination with the FOLFIRI regimen as a first-line treatment for patients with KRAS wild-type, EGFR-positive metastatic colorectal cancer. The approval for this new indication was supported by a retrospective analysis of the phase III CRYSTAL trial, which showed a 4-month increase in median survival for patients without KRAS mutations who received cetuximab plus FOLFIRI versus FOLFIRI alone.

Further reading: “Colorectal Cancer Trials Support Gene Testing for Two Drugs

Public Workshop Focuses on New Guidelines for Pediatric Imaging Devices

On July 16, the Food and Drug Administration (FDA) held a public workshop to gather comments on a draft guidance that encourages manufacturers to consider the safety of children in the design of new x-ray imaging devices. The draft guidance addresses the development, marketing, and use of imaging devices, including design features, labeling information, and testing in children.

Children are more sensitive than adults to radiation, including the low levels of radiation delivered by imaging machines such as computed tomography (CT) scanners and fluoroscopy devices, which use x-rays to see inside the body. A recent study showed that radiation exposure from CT scans in childhood results in very small but increased risks of leukemia and brain tumors in the first decade after exposure.

The FDA developed the new draft guidance as part of its Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging. The agency launched the initiative in 2010 in response to rising concern about the contribution of medical radiation to exposures in the general population and after several reports of patients receiving accidental radiation overdoses during routine imaging.

The new draft guidance includes recommendations from a March 2010 public meeting on how to improve safety for pediatric patients undergoing medical imaging. Participants at that meeting recommended the development of tailored pediatric protocols and control settings by device manufacturers, better instructions and educational materials for device operators, an overall emphasis on reducing pediatric doses, and better tools for quality assurance and for the collection and storage of information on individual patients’ doses.

Participants at the workshop included members of the Alliance for Radiation Safety in Pediatric Imaging, professional organizations such as the American Association of Physicists in Medicine, industry representatives of the Medical Imaging and Technology Alliance, and members of the general public.

The participants discussed a number of issues, including

  • the need to use patient size rather than age to guide the development of pediatric imaging protocols;
  • the need for better training, since the majority of pediatric imaging scans are not performed in dedicated children’s facilities;
  • questions about whether simulation alone is sufficient to test new devices and protocols, or whether clinical data from children are needed;
  • the need for better communication between manufacturers and the medical staff who use the machines; and
  • concerns about whether restrictive product labeling would lead to the off-label use of machines with no safety or efficacy data available for children.

The FDA will accept comments on the draft guidance until September 7. Instructions on how to submit comments by mail or through can be found on the FDA’s draft guidance webpage. The draft guidance docket number is FDA-2012-D-0384.

An archived webcast of the public workshop is available, and full transcripts of all sessions will be made available, on the workshop webpage.

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