FDA Approves Osimertinib for Advanced EGFR-Mutated NSCLC After Chemoradiation
U.S. Food and Drug Administration approved osimertinib (Tagrisso) for adults with locally advanced, unresectable stage III non-small cell lung cancer (NSCLC) who have not experienced disease progression during or after platinum-based chemoradiation therapy and whose tumors contain EGFR exon 19 deletions or exon 21 L858R mutations.
The decision was based on the results of the double-blind, randomized, placebo-controlled LAURA clinical trial, a phase 3 study that included 216 adults. Participants had locally advanced, unresectable stage III NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. In addition, their disease had not progressed during or after treatment with definitive platinum-based chemoradiation within 42 days before the study’s randomization period.
Participants were randomly assigned in a 2:1 manner to receive either osimertinib (80 mg orally once daily) or placebo. Patients received treatment until the occurrence of disease progression or unacceptable toxicity. Progression-free survival (PFS) was the study’s primary endpoint and was assessed by blinded independent central review. Overall survival (OS) was an additional endpoint.
Osimertinib elicited a statistically significant PFS benefit compared with placebo, with a hazard ratio of 0.16 (95% confidence interval [CI], 0.10–0.24; P<.001). The median PFS was 39.1 months (95% CI, 31.5 months to not estimable) in the osimertinib group versus 5.6 months (95% CI, 3.7–7.4 months) in the placebo group. OS results were not mature at the time of the final analysis. However, there was no trend toward determent, with 36% of prespecified deaths reported in the analysis.
Results of the LAURA trial were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Experts at the conference said that osimertinib could replace standard chemoradiotherapy followed by durvalumab in this patient population.
“Based on these results, osimertinib will become the new standard of care for patients with locally advanced non-small cell lung cancer following definitive chemoradiation,” said Suresh S. Ramalingam, MD, of the Winship Cancer Institute at Emory University in Atlanta, during the meeting. “EGFR mutation testing should be conducted for patients with stage III disease in order for patients to achieve optimal outcomes.”
Osimertinib, a tyrosine kinase inhibitor, is indicated for EGFR-mutated NSCLC in the metastatic setting and in the early-stage setting for NSCLC after resection. The recommended dose for osimertinib is 80 mg. It can be taken once per day, with or without food, and can be continued until disease progression or unacceptable toxicity occurs.
