Diagnostics & Imaging Week Associate

Genzyme (Cambridge, Massachusetts) reported the commercial availability of a new laboratory test to help identify patients likely to respond to therapies targeted for the treatment of non-small cell lung cancer (NSCLC).

Genzyme’s EGFR Mutation Assay will help to detect the presence of epidermal growth factor receptor (EGFR) mutations in patients with NSCLC.

EGFR mutations have been shown to correlate with clinical response to certain drugs, including Tarceva (erlotinib) and Iressa (gefitinib), used in treating this deadly form of cancer.

According to Mara Aspinall, president of Genzyme Genetics (Westborough, Massachusetts), the company division responsible for developing these tests, this and other targeted diagnostics for cancer are part of a growing trend to help physicians determine the best course of treatment for a patient as soon after a diagnosis is made as possible.

“With this test, the rationale for prescribing specific lung cancer therapies may be individualized and we can help physicians and patients choose the best treatment possible,” she told Diagnostics & Imaging Week. “This is ‘personalized medicine’ in action.”

Currently, the first line of treatment for NSCLC is chemotherapy, but many patients do not respond to that treatment, causing a doctor to have to move on to the next line of treatment.

Certain therapies, including Tarceva and Iressa, are currently used in NSCLC patients who are refractory, or have failed, one or more chemotherapy regimens. Refractory patients make up about 30% of the total NSCLC patient population.

Clinical studies of Tarceva and Iressa in the first-line setting are ongoing. Mutation testing may allow these drugs to achieve approved indications for first-line use in NSCLC patients who have the EGFR mutations and are, therefore, more likely to respond to these therapies.

“Up to 20% of patients with non-small cell lung cancer test positive for the EGFR mutation,” said Aspinall, adding that “for these patients, physicians now have additional information to decide how aggressively and when they should use these other targeted treatments.” Tests like this, she said, “give the physician the ability to have more data and not be forced into ‘trial-and-error medicine’ in the treatment of cancer patients.”

Using the trial-and-error approach, she said, costs not only in economical terms, but also costs patients in terms of needless added toxicity.

Indeed, time is of the essence in treating cancer patients, particularly those with lung cancer. According to the American Cancer Society (Atlanta), lung cancer is the leading cause of cancer death for both men and women, with a five-year relative survival rate for all stages of about 15%. An estimated 163,000 people in the U.S. die of this disease each year, which is more than the number of those who die each year from colon, breast, and prostate cancers combined. In 2005, there will be an estimated 172,570 new cases of lung cancer in the U.S.

With diagnostic tests like the EGFR mutation assay, Aspinall said, “you have the opportunity to choose therapies that are more likely to work for these individuals.”

The discovery of the EGFR mutations was made by researchers at Dana-Farber Cancer Institute and Massachusetts General Hospital (both Boston).

Physicians analyzed tumor samples from lung cancer patients who had responded to tyrosine kinase inhibitors of EGFR. According to their published studies, the majority of patients who responded to therapy had the mutations. Genzyme holds exclusive, worldwide diagnostic rights to their discovery of EGFR gene mutations in NSCLC tumors.

“The availability of the EGFR test will give physicians and lung cancer patients critical information to help them determine the most appropriate course of treatment,” said Thomas Lynch, MD, director of the Center for Thoracic Cancers at Mass General, who was involved in the discovery of the EGFR mutation. “We expect to see more informed treatment decisions emerge now that responders can be identified. As a result, we hope that patients undergoing therapy will benefit from a longer survival time.”

“Knowing at the onset whether a lung cancer patient is likely to benefit from a specific therapy is a significant advance in the treatment of lung cancer,” said Matthew Meyerson, MD, PhD, associate professor of pathology at Dana-Farber, who also was involved in the discovery of the EGFR mutation. “This test is an important first step in the development of rational and tailored lung cancer therapies.”

Researchers are now investigating the presence of the same EGFR mutations in other tumor types to determine if mutation testing can help bring effective, targeted therapies to patients suffering from other cancers.

EGFR Mutation Analysis combines PCR and gene sequencing testing technologies for the detection of somatic mutations in NSCLC tumor tissue. To perform the test, cells from specific tumor-rich areas are microdissected, followed by DNA extraction, polymerase chain reaction amplification, and bi-directional sequencing of exons 18 through 21 in tyrosine kinase domain of the EGFR gene.

Genzyme’s EGFR mutation analysis is performed in Genzyme’s CLIA-certified high complexity molecular testing laboratory in Westborough. A team of 17 surgical pathologists and PhD geneticists review the EGFR mutation analyses and are available for personal consultations as needed.

This EGFR assay is one of several major new cancer diagnostic tests Genzyme Genetics plans to launch this year, all of which are designed to help identify patients likely to respond to targeted cancer therapies.

In July, the company unveiled its first cancer test to complement the treatment Campath (alemtuzumab). The new test identifies low levels, known as minimal residual disease, of B-cell chronic lymphocytic leukemia.

According to Aspinall, there are a lot of new cancer drugs coming down the pipeline, and she said she believes the model of having a diagnostic that gives the physician additional information in addition to their clinical evaluation is a very powerful one and will be more and more necessary as drugs in the pipeline come to fruition.

“These tests help target drugs to ensure that it’s the right drug for the right patient at the right time,” she said.