Positive findings from the FLAURA2 study add to the body of evidence supporting treatment with osimertinib for patients with EGFRm non–small cell lung cancer.
The combination of osimertinib (Tagrisso) with chemotherapy generated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs osimertinib alone for the treatment of patients with locally advanced or metastatic EGFR-mutated (EGFRm) non–small cell lung cancer (NSCLC), according to results from the phase 3 FLAURA2 trial (NCT04035486).1
In addition, the safety data and discontinuation rates due to adverse events observed with the combination were consistent with the established profiles of each agent alone. The overall survival (OS) data were immature at the time of this analysis and will be formally assessed at a subsequent analysis.
These findings add to the body of evidence supporting osimertinib for the treatment of patients with EGFRm NSCLC, as it has shown to improve outcomes in patients with early-stage disease in the phase 3 ADAURA trial (NCT02511106), as well as now in this trial for patients with late-stage disease.
"This is an exciting outcome for patients with advanced EGFR-mutant lung cancer. It builds on the success of osimertinib, which is the current standard of care for patients with advanced EGFR-mutant cancer. The data from the FLAURA2 trial demonstrate a further improvement in outcomes when chemotherapy is combined with osimertinib," Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, told Targeted OncologyTM. "Osimertinib is an small molecule epidermal growth factor receptor tyrosine kinase inhibitor."
Osimertinib has also shown proven clinical activity in treating central nervous system metastases across settings.
The FLAURA2 study enrolled 587 patients into the trial, including some in the safety run-in portion of the trial, and the main trial where patients received osimertinib alone or in combination with chemotherapy.2 A screening period, treatment period, and follow-up period were utilized in the study.
Patients were treated with either osimertinib alone at 80 mg daily or osimertinib 80 mg in combination with pemetrexed at 500 mg/m2 plus cisplatin at 75 mg/m2 or carboplatin on day 1 of each 21-day cycle for 4 cycles, followed by osimertinib daily with pemetrexed maintenance at 500 mg/m2 every 3 weeks.
Enrollment in the study was open to male or female patients aged 18 years or older, and patients from Japan were required to be at least 20 years of age. Patients were required to have pathologically confirmed non-squamous NSCLC, and NSCLC of mixed histology was allowed. Patients with newly diagnosed locally advanced or metastatic NSCLC or recurrent NSCLC not amenable to curative surgery or radiotherapy were also eligible for enrollment in the study.
Further, eligibility was open to patients whose tumor harbored 1 of the 2 common EGFR mutations, those who had untreated advanced NSCLC not amenable to curative surgery or radiotherapy, a WHO performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks, and a life expectancy >12 weeks at day 1.
The primary end point assessed in the trial was PFS, and secondary end points included OS, objective response rate, duration of response, depth of response, disease control rate, PFS2, and pharmacokinetics.
Further data from the trial will be presented at an upcoming medical meeting and shared with global health authorities.
"Next steps include additional analyses on the trial, including whether the combination is effective at treating brain metastases or delays the occurrence of brain metastases above and beyond what is known for osimertinib by itself," added Jänne.
“These significant FLAURA2 results show [osimertinib] has the potential to offer patients in the first-line setting a new treatment option that can extend the time they live without their disease progressing. This meaningfully builds on successive trials which have demonstrated improved clinical benefit with Tagrisso in patients with EGFR-mutated lung cancer,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in a press release.1