PET TO FIND LUNG CANCER RESPONSIVE TO ERLOTINIB?

July 7, 2011 (Amsterdam, the Netherlands) — An innovative and noninvasive method of finding out whether a lung tumor harbors EGFR mutations, and therefore might be responsive to erlotinib, was reported here at the 14th World Conference on Lung Cancer.
EGFR inhibitors such as erlotinib (Tarceva) are now considered the best treatment option for patients with nonsmall-cell lung cancer (NSCLC) whose tumors harbor EGFR mutations. To find out whether the patient has such mutations, testing must be carried out on tumor tissue, which can take several days. In addition, obtaining adequate samples of tumor tissue is not easy.
The new method reported here involves positron emission tomography (PET) scanning using a radiolabeled tracer, [¹¹C]erlotinib, and takes only a couple of hours. Although the technique has been tested in only 10 patients, this study was selected for the presidential session featuring the best oral presentations. Discussant Luis Paz-Ares, MD, PhD, chair of oncology at Seville University, Spain, praised the researchers for their innovation, and said the approach is important because "we do not always have tissue for testing...yet we know that for these patients [with EGFR mutations], this is the best therapy."
There are other research efforts underway to find noninvasive ways of identifying mutations. Some aim to do this with a blood sample — using monoclonal antibodies directed against mutations or focusing on circulating tumor cells. However, these efforts are still in the very early stages, whereas the PET technique has already been tested in patients.
High Uptake of the Tracer
The study was headed by Idris Bahce, MD, from the VU University Medical Center in Amsterdam, the Netherlands. It was conducted in 10 patients with NSCLC, 5 of whom had activating EGFR mutations and 5 of whom had wild-type EGFR, as determined by DNA sequencing of tumor tissue.
Study Limitations Are Important
All patients underwent a low-dose computed tomography scan, followed by a 10-minute radiolabeled water dynamic PET scan to check tumor perfusion, Dr. Bahce explained. Then they underwent the 1-hour radiolabeled erlotinib dynamic PET scan; from this, scan data were analyzed for the uptake of the tracer into the tumor.
Patients with EGFR mutations showed a significantly higher uptake of radiolabeled erlotinib than patients without these mutations; the water scans showed that this difference was not due to differences in tumor perfusion.
In addition, the higher uptake of the tracer correlated with tumor response in subsequent erlotinib tumors; only the high-uptake tumors responded to treatment, Dr. Bahce reported.
"We found that patients who had an activating EGFR mutation also had an increased tracer uptake and were more sensitive to treatment with erlotinib, compared with those who did not have this mutation," Dr. Bahce noted. This new imaging technique offers a noninvasive predictive marker that identifies NSCLC patients who benefit from treatment with EGFR inhibitors, he said.
Such tools are needed because there are patients for whom adequate tissue is difficult to obtain, explained Dr. Paz-Ares. He also pointed out that more work is needed on this approach.
"This is a proof-of-concept study, " he said, and now the technique needs to be refined and more patients must be tested to calculate negative and positive predictive values.
One limitation that Dr. Paz-Ares drew attention to is that the radiolabeled tracer used, [¹¹C]erlotinib, has a short half-life, so it needs to be made and used in the same center. "This is what we did," Dr. Bahce said, adding that their center has a cyclotron so they were able to do so. This is fine for research, said Dr. Paz-Ares, but it is not very practical for clinical practice.
Another limitation is that this study focused on the EGFR mutation on exon 19, so it will have to be repeated with other known EGFR mutations (such as exon 21) to see if the technique also works with those, Dr. Paz-Ares noted.
There are numerous other mutations being identified in NSCLC, so there will always be a need for tumor-tissue testing, he added.
Dr. Bahce and Dr. Paz Ares have disclosed no relevant financial relationships.
14th World Conference on Lung Cancer (WCLC): Abstract 1910. Presented July 6, 2011.