FDA Expands Approval for Osimertinib T790M Companion Diagnostic Blood Test

October 4, 2016

The US Food and Drug Administration has approved a plasma sample label extention for the T790M companion diagnostic blood test, cobas® Mutation Test v2.

The US Food and Drug Administration (FDA) has approved a plasma sample label extention for the T790M companion diagnostic blood test, cobas® Mutation Test v2, with osimertinib (Tagrisso) administration, AstraZeneca announced. The test noninvasively detects the T790M epidermal growth factor receptor gene (EGFR) mutation in metastatic non-small cell lung cancer (NSCLC).

The FDA’s approval represents “a tremendous step forward” for patients whose lung cancers have progressed on EGFR TKI drugs, or for whom biopsy may not be possible, said Andrew Coop, Vice President of US Medical Affairs, Oncology, at AstraZeneca, in a press release.

The T790M (Thr790Met) EGFR mutation involves an amino acid substitution in exon 20. Osimertinib, an 80 mg once-daily, oral third-generation tyrosine kinase inhibitor (TKI), targets the T790M EGFR mutation.

Overall, 10% to 15% of NSCLCs are EGFR mutation-positive. “Nearly two-thirds” of EGFR mutation-harboring NSCLCs eventually progress on first-generation EGFR TKIs because of an acquired T790M mutation, according to AstraZeneca. Osimertinib received accelerated approval from the FDA in November 2015, based on tumor response rates and durations, for the treatment of patients faced with T790M-harboring metastatic NSCLC. It is currently the only FDA-approved drug for this indication.

The T790M companion test was developed in multiple studies including the phase I and II AURA trials. It can be performed using plasma or tissue samples, which are “broadly concordant,” the company reported. Tumor heterogeneity or assay methodology issues can cause discordant results; a positive T790M finding with tissue from patients eligible for biopsy may mean that a patient is eligible for treatment with osimertinib despite a T790M-negative blood test result, the company noted.

Osimertinib-related adverse events included grade 3/4 diarrhea (1% of patients; 42% all grades) and rash (41% all grades; 0.5% grade 3/4). No grade 3/4 dry skin or nail toxicity were noted, but occurred frequently at grades 1 and 2 (31% and 25%, respectively).

Interstitial lung disease (ILD)/pneumonitis occurred in 3.3% of patients and were associated with four patient deaths (0.5% of patients), the company reported. Cardiomyopathy occurred in 11 patients (1.4%), including two fatal cases.

For patients who develop dyspnea, cough, and fever, osimertinib administration should be suspended and ILD investigated immediately; for confirmed cases of ILD, osimertinib should be permanently discontinued.

For patients with symptomatic congestive heart failure or persistent asymptomatic left ventricular dysfunction that fails to resolve within 4 weeks, osimertinib should be permanently discontinued, AstraZeneca advised.

There are no reported contraindications for osimertinib.