Osimertinib Approved for Locally Advanced, Unresectable Stage III Non–Small Cell Lung Cancer Following Chemoradiation Therapy
Expert Perspectives · Lyn Brook · 2024-09-26
The FDA has granted approval to osimertinib (Tagrisso®, AstraZeneca Pharmaceuticals) for adult patients with locally advanced, unresectable stage III non–small cell lung cancer (NSCLC) whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
Why it matters: “Osimertinib is a recommended treatment for advanced NSCLC with an EGFR mutation and as adjuvant treatment for resected EGFR-mutated NSCLC,” wrote Shun Lu, MD, PhD, Director of the Oncology Department and Professor at Shanghai Chest Hospital, Shanghai Jiaotong University, and colleagues, in their published results of the LAURA trial (NCT03521154), on which approval was based. “EGFR tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC.”
What they studied: Efficacy was measured in the phase 3, double-blind, placebo-controlled trial which enrolled 216 adult patients with locally advanced, unresectable stage III NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who had not progressed during or following definitive platinum-based chemoradiation within 42 days prior to study randomization. Patients were randomized 2:1 to receive either 80 mg of osimertinib orally once daily or placebo until disease progression or unacceptable toxicity.
The primary efficacy outcome measured was progression-free survival, as assessed by Blinded Independent Central Review (BICR). A key secondary efficacy outcome measured was overall survival.
What they found: At the time of analysis, a statistically significant improvement in progression-free survival was demonstrated in the osimertinib arm compared with those receiving placebo. Progression-free survival was seen at a median of 39.1 months in the osimertinib arm compared with 5.6 months in the placebo arm. Overall survival results were immature at the time of analysis—36% of pre-specified deaths were reported for the final analysis—yet no trends towards a detriment were observed.
Adverse events: The most common adverse events, including laboratory abnormalities experienced in ≥20% of patients receiving osimertinib were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.
Conclusion: “Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC,” concluded Dr. Lu and colleagues.
Instructions: The recommended dosage of osimertinib is 80 mg once daily, with or without food, until disease progression or unacceptable toxicity.