Blood, Urine Tests for EGFR as Alternatives to Lung Biopsy

Zosia Chustecka

April 22, 2015

Newly diagnosed patients with advanced non-small cell lung cancer (NSCLC) should have a tumor biopsy sent off for testing for epidermal growth-factor receptor (EGFR) mutation status.

About 10% to 15% of NSCLC patients in Europe and 30% to 40% in Asia have tumors that harbor EGFR mutations, and clinical trials have shown that these patients have better outcomes when they are treated first-line with an EGFR inhibitor instead of chemotherapy.

However, it can be difficult to obtain sufficient lung tumor tissue for testing. In such cases, a new blood test can be used instead, suggest the results from a "real world" study presented last week at the 2015 European Lung Cancer Conference in Geneva.

The study, known as ASSESS, was funded by AstraZeneca, which markets the EGFR inhibitor gefitinib (Iressa). It enrolled 1311 patients with advanced NSCLC in clinical practices across Europe (n = 1288) and Japan (n = 291), and compared the results obtained from a blood test (developed by Qiagen) that measures EGFR mutations in plasma circulating tumor (ct)DNA with those obtained from tumor tissue testing.

In 1162 matched samples, there was good agreement between tumor and plasma test results for EGFR mutation status (89%; 95% confidence interval, 87 - 91).

However, plasma testing only identified approximately half of patients with EGFR mutations found by tumor testing, the researchers report.

But the blood test identified EGFR mutations in some patients with EGFR mutations missed by tumor testing; failure to identify EGFR mutations with tumor testing was associated with use of less sensitive methodology, the researchers note.

Lead author Martin Reck MD, PhD, from the Department of Thoracic Oncology at Lungen Clinic Grosshansdorf in Germany, said in a statement that the study confirms that tumor testing is currently the best way of identifying patients with EGFR mutations, but it also shows "that plasma ctDNA testing is a viable alternative to tumor testing when tumor samples are unavailable, provided that optimal DNA extraction and appropriately sensitive methodology are used."

He added that the results also show "that improvements can still be made in tumor testing to ensure all patients with an EGFR mutation are identified and given appropriate treatment."

Another study presented at the same meeting found that 25% of advanced NSCLC patients do not undergo testing for EGFR mutation status, which may be denying them the chance of a better treatment for their disease.

The use of this blood test for ctDNA assessment of EGFR mutation status in patients where a tumor sample is not evaluable was recently approved for use with gefitinib in Europe and in China.

Gefitinib is not available in the United States, but AstraZeneca says it is working with Qiagen to develop use of the test in the United States in order to guide gefitinib treatment.

Urine Test Identifies T790M Mutation

Also presented at the meeting were clinical data showing that a urine test can be used to identify patients with EGFR mutations being treated with EGFR inhibitors who have developed a second mutation that causes drug resistance. When these patients develop the T790M mutation, they stop responding to EGFR therapy.

Several new drugs, including AZD9291 from AstraZeneca, have been developed specifically to overcome this T790M mutation, and early clinical trial data suggest that they show benefit when used in patients with this mutation who are progressing on EGFR drugs.

The urine test, developed by Trovagene Inc., measures urinary ctDNA.

At the meeting, results with this test were presented from an interim analysis of data from 34 patients who are taking part in an ongoing trial; these patients had metastatic NSCLC and had progressed on erlotinib (Tarceva, OSI/Astellas).

The results show that the urine test correctly identified six of six patients who were already known to have developed the T790M mutation from tissue biopsy testing. But it also identified a few additional patients who had the T790 mutation but had negative biopsy results or had not yet undergone biopsy.

"These interim results suggest that use of urinary ctDNA has potential to detect EGFR T790M status in a higher number of study subjects and may make some patients eligible for therapy who would by tissue biopsy be falsely classified as negative," lead author Hatim Husain, MD, from the University of California, San Diego Moores Cancer Center, commented in a statement.

The urine test detected EGFR T790M resistance mutations months earlier than radiologic detection of progression in patients, he noted, adding, "This has the potential to enable physicians to better align therapeutic selection and inform early therapeutic decision making."

Dr Reck reports being on the speakers bureau for AstraZeneca and many other pharmaceutical companies. Two of his coauthors are employees of AstraZeneca.

2015 European Lung Cancer Conference (ELCC): Abstracts 350_PR and 360. Presented April 17, 2015.


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