FDA Approves Novel Diagnostics for NSCLC, NETs

Alberto Gutierrez, PhD

The FDA has approved two separate diagnostic tests for patients with cancer—one that detects somatostatin receptor-positive neuroendocrine tumors (NETs) and another for the detection of EGFR mutations from blood samples for patients with non—small cell lung cancer (NSCLC).

The blood test, cobas EGFR Mutation Test v2, was approved as a companion diagnostic for erlotinib (Tarceva) and can be used for the detection of the EGFR exon 19 deletion or L858R mutation. If findings from the blood test are negative, the FDA suggests that a tumor biopsy should be conducted, to confirm the results. The availability of a noninvasive technique could help increase the rates of mutation testing for patients with NSCLC.

“Approvals of liquid biopsy tests make it possible to deliver highly individualized healthcare for patients,” Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in a statement. “Liquid biopsies also have the potential to allow physicians to identify patients whose tumors have specific mutations in the least invasive way possible.”

The approval of the EGFR test was marked as the first-ever for a blood-based genetic test. The efficacy of the blood-based test, which can also be utilized on tumor tissue samples, was confirmed through a comparison of results from the new diagnostic with findings from the tissue-based cobas EGFR Mutation Test v1. In November 2015, the diagnostic was also approved for the detection of EGFR T790M alterations as a companion diagnostic for osimertinib (Tagrisso).

“As more targeted therapies become available, it is critical that we provide innovative molecular testing methods that make it easier for patients to get tested, regardless of the surgery risks or tumor tissue availability,” Roland Diggelmann, chief operations officer at Roche Diagnostics, which is the company manufacturing the test, said when the new diagnostic was launched in 2015. “By investing in liquid biopsy research and developing the cobas EGFR Mutation Test v2 for use with either plasma or tissue samples, Roche is helping to remove these common barriers from molecular testing.”

The NET diagnostic kit, known as Netspot, contains a radioactive agent for use in conjunction with PET imaging. The kit includes a single-dose injection of gallium (Ga)-68 Dotatate, which binds to somatostatin receptors. The agent, which was approved under the FDA's priority review program, allows for better identification and measurement of NETs compared with existing options.

"Use of advanced imaging techniques to detect rare neuroendocrine tumors at an early stage in patients is critical," Libero Marzella, MD, PhD, director of the Division of Medical Imaging Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “Netspot provides another diagnostic tool whose results will help clinicians determine the location and extent of the tumor. This information is important for planning the appropriate course of therapy.”

The approval for Ga-68 Dotatate was based upon findings from 3 separate clinical trials. The first compared images obtained using Ga-68 Dotatate with those using other imaging drugs. In the study, the superiority of Ga-68 Dotatate was confirmed using CT or MRI. A second study evaluated the efficacy of Ga-68 Dotatate using histopathology or clinical follow up, and the third looked specifically at patients with NET recurrence.

The FDA noted that use of Ga-68 Dotatate adds to overall long-term cumulative radiation exposure. Following administration of the test, frequent liquid consumption and urination is encouraged, to flush the drug from the patient's system. In studies, serious adverse reactions were not identified.

In addition to the current approval, the Ga-68 Dotatate kit is also being considered as a potential companion diagnostic for the peptide receptor radionuclide therapy Lu-Dotatate (177Lutetium DOTATATE; Lutathera). An application for Lu-Dotatate has been submitted to the FDA for approval consideration, with a priority review anticipated. The application was based on findings from the phase III NETTER-1 trial, which showed a 79% reduction in the risk of progression or death with the radionuclide versus high-dose octreotide LAR for patients with mid-GU NETs.

In the phase III trial, median progression-free survival was not reached with Lu-Dotatate versus 8.4 months with octreotide (HR, 0.21; 95% CI, 0.13-0.33; P <.0001). All patients in the study were somatostatin receptor-positive. The response rate was 18% with Lu-Dotatate versus 3% with octreotide (P = .0008).

“This is a population of patients with midgut neuroendocrine tumors that has been highly resistant to systemic treatments, at least as far as response rate is concerned,” lead author Jonathan R. Strosberg, MD, a medical oncologist with Moffitt Cancer Center, said when he presented updated findings at the 2016 GI Cancers Symposium. “This is the only study to show a double-digit objective response rate in this population.”

Advanced Accelerator Applications, the developer of Lu-Dotatate, announced that it had completed submission of the application on April 29, 2016. Given regular approval timelines, the FDA is expected to make a final decision on the application for Lu-Dotatate within the next 6 to 8 months.

Strosberg JR, Wolin EM, Chasen B, et al. NETTER-1 phase III: Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-LU-Dotatate. J Clin Oncol. 2016;34 (suppl 4S; abstr 194).