National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
April 20, 2010 • Volume 7 / Number 8

FDA Update

Erlotinib Approved as Maintenance Therapy for Non-small Cell Lung Cancer

Last week, the FDA approved erlotinib (Tarceva) to prevent the recurrence of non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after receiving initial treatment with platinum-based chemotherapy. Maintenance therapy is a new approach intended to capitalize immediately on a drug’s initial chemotherapeutic success rather than waiting for cancer to return or progress, which can be especially problematic in lung cancer.
This approval is based on the results of the SATURN trial, an international phase III clinical trial of approximately 889 patients with advanced NSCLC. Patients in the trial were given four cycles of first-line platinum-based chemotherapy; those whose cancer did not progress were then randomized to receive erlotinib or a placebo. Patients who received erlotinib had a median 1.2-week improvement in progression-free survival (12.3 weeks versus 11.1 weeks) and a median 1-month improvement in overall survival (12 months versus 11 months).

Erlotinib, which targets the EGFR pathway, was originally approved in 2004 to treat locally advanced or metastatic NSCLC that had spread after at least one course of chemotherapy. The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12-1 against this Supplemental New Drug Approval in December 2009.

The acting chair of the ODAC panel in December 2009, Dr. Wyndham Wilson of NCI’s Center for Cancer Research, explained that when a drug such as erlotinib has been shown to be effective in patients whose cancer progresses, it is incumbent on researchers to show in a clinical trial that there is an independent advantage to using the drug in the earlier, maintenance setting.

“If control patients are not crossed over to erlotinib when their disease begins to progress,” Dr. Wilson said, “any benefit observed in the maintenance arm may simply be due to drug access, which is not available to the control patients. Importantly,” he continued, “if the drug is not significantly more beneficial when given as maintenance therapy versus at the time of disease progression, many patients in the maintenance arm will be unnecessarily overtreated and risk potentially serious side effects, such as blood clots, and the inconvenience of treatment.”

Long-term Shortage of Cancer Drug Mustargen Expected

The FDA has issued a drug shortage warning for mechlorethamine HCl (Mustargen), which is approved for the treatment of advanced Hodgkin disease and a number of hematologic and other cancers. According to Lundbeck, Inc., the sole manufacturer, the drug will be in short supply for up to a year because of manufacturing problems.

A limited supply will become available in mid- to late-April, with preference given to patients who are currently receiving the drug for therapy. Pharmacies and physicians are advised to contact their distributor or wholesaler in order to meet the needs of those patients, and then to develop an orderly transition to alternative therapies.

It is the FDA’s policy to help prevent or alleviate shortages of medically necessary drugs that could significantly impact public health. The agency “has searched but is unaware of any other supplies of mechlorethamine HCl available from any other sources at this time,” and advised that alternative treatment plans should be made for patients who have been recently prescribed Mustargen.

Changes Announced in Approval Process for Certain Radiation Therapy Devices

On April 8, the FDA sent a letter to manufacturers of linear accelerators (machines that create radiation used in cancer therapy), radiation therapy treatment planning systems, and ancillary devices with a notification that their products may no longer be eligible for third-party review as part of the premarket 510(k) approval process. In the 510(k) approval process, manufacturers must show that their new product is at least as safe and effective as a similar, legally marketed device.

Third-party 510(k) review for biomedical devices was introduced as a money-saving strategy in the FDA Modernization Act of 1997, and it allows device manufacturers to have accredited, non-federal organizations review their approval applications, leaving only the final decision to the FDA. However, the process has recently come under scrutiny for potentially being too lenient.

The FDA “is taking several steps to improve the safety and safe use of certain radiation therapy devices,” including restrictions on third-party review, wrote Dr. Jeffrey Shuren, director of the FDA’s Center for Devices and Radiological Health, in the April 8 letter. Between December 31, 1999, and February 18, 2010, the FDA received 1,182 Medical Device Reports for radiation therapy devices that “revealed device problems that appear to be the result of faulty design or use error that could be mitigated by the incorporation of additional safeguards,” wrote Dr. Shuren.

Linear accelerators accounted for 74 percent of these error reports, radiation therapy treatment planning systems accounted for 19 percent, and ancillary devices, including proton therapy machines and radiation therapy simulators, accounted for 7 percent. Software problems triggered 362 of the error reports overall.

The FDA is planning to hold a public workshop on radiation therapy treatment planning, medical linear accelerators, and ancillary devices. Topics for discussion will include new safeguards; changes in premarket device testing to provide appropriate assurances of safety and effectiveness (particularly for software); and premarket review for modifications to software. The date and time of the workshop will be announced in the Federal Register.