Mark A. Socinski, MD, discusses how the FLAURA trial led to the adoption of osimertinib for patients with non–small cell lung cancer and EGFR mutations.
Mark A. Socinski, MD, a medical oncologist and executive director (thoracic cancer) at the AdventHealth Cancer Institute, discusses how the FLAURA trial (NCT02296125) led to the adoption of osimertinib (Tagrisso) for patients with non–small cell lung cancer (NSCLC) and EGFR mutations.
According to Socinski, this trial enrolled patients with EGFR exon 19 deletion and L858R mutations who were previously untreated. Patients were randomly assigned to receive either osimertinib or a first-generation EGFR-tyrosine kinase inhibitor [EGFR-TKI] of physician’s choice: erlotinib (Tarceva) or gefitinib (Iressa).
The primary end point was progression-free survival (PFS), which was met in the primary analysis with a median PFS of 18.9 months for osimertinib versus 10.2 months for the comparator arm (HR, 0.46; 95% CI, 0.37-0.57; P < .001). Socinski says that this drug is very effective in patients with a T790M mutation, which is associated with resistance to earlier-generation EGFR-TKIs. There was also an overall survival (OS) advantage reported. This trial changed the standard of care for patients with EGFR mutations, Socinski says.
0:08 | The FLAURA trial took [patients with] the common mutations, [EGFR] exon 19 [deletion] and L858R, first-line, previously untreated, good performance status patients and randomized them into a control arm, which was the choice of one of the first-generation drugs, either erlotinib or gefitinib. Most patients on the control arm—it was physician choice—most patients got gefitinib since that's the one most commonly used outside the United States. I believe all the patients accrued in the United States received erlotinib. These are both first-generation drugs. In the investigational arm was osimertinib. The primary end point was PFS.
0:53 | The trial was, I would say wildly positive in favor of osimertinib because it's a better mutation drug. It is a very good T790M drug. And it is somewhat less inhibitory to wild-type EGFR. So it has both an activity as well as a toxicity advantage in this setting. The PFS, which was the primary end point, was about doubled from about 10 months or so to about just shy of 19 months. The HR I believe was 0.46 so [it was] statistically and clinically significant. There was also an OS advantage associated with osimertinib, so it clearly changed the standard of care in the first-line setting.