Safety outcomes with osimertinib in the phase III LAURA study

An in-depth safety analysis from the phase III LAURA study demonstrated that the safety profile of osimertinib after definitive chemoradiotherapy was as expected and manageable. The majority of radiation pneumonitis events were mild to moderate in severity and could be managed effectively per protocol-mandated guidelines.

In the phase III LAURA study, osimertinib given post-definitive chemoradiotherapy (CRT) previously demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit vs. placebo in patients with unresectable stage III EGFR‑mutated NSCLC without progression during/after CRT. At WCLC 2024, Kato et al. reported an in-depth safety analysis from the LAURA study.

Study design

This phase III double-blind study enrolled patients with locally advanced, unresectable stage III EGFRm NSCLC with no progression during or following definitive chemoradiotherapy. These patients (n=216) were randomised 2:1 to receive either osimertinib (80mg QD), or placebo (QD). Treatment was continued until BICR-assessed disease progression, toxicity or other discontinuation criteria were met. Open-label osimertinib was offered to both treatment arms after BICR-confirmed progressive disease. The primary endpoint was progression-free survival (PFS) by BICR, and key secondary endpoints were overall survival (OS), central nervous system (CNS) PFS, and safety.

Results

At the time of data cut-off, the median total and actual exposures were 24.0 and 23.7 months for osimertinib and 8.3 and 7.9 months for placebo, respectively. The safety profile for patients aged less than 65 and those aged 65 or over was similar across treatment arms. For patients in the osimertinib arm, 33% and 37% experienced a grade ≥3 adverse event (aged <65 and ≥65, respectively), compared to 13% and 12% in the placebo arm. Furthermore, 58% and 53% of patients receiving osimertinib had an adverse event leading to dose interruption, while 28% and 21% of patients in the placebo group experienced this, aged <65 and ≥65, respectively. These figures for dose reduction in the osimertinib arm were 4% and 15% compared to 0 and 3% in the placebo group. Adverse events leading to discontinuation were observed in 9% of patients receiving osimertinib <65 years of age compared to 18% in those aged over 65, while this was 3% and 9% in the placebo group, respectively.

Radiation pneumonitis (grouper term) was reported in 48% of patients in the osimertinib group vs. 38% in the placebo arm. Most dose interruptions due to adverse events were driven by radiation pneumonitis (32% osimertinib arm vs. 14% placebo). Of the 69 osimertinib-treated patients with radiation pneumonitis (grouped term), 32% continued treatment without dose modification, 62% interrupted treatment and subsequently restarted, and 6% permanently discontinued treatment; 87% continued osimertinib without recurrence of radiation pneumonitis. Interstitial lung disease (grouped term) was reported by 8% of osimertinib-treated patients; grade 3 (1%), grade 5 (<1%).

Conclusion

The safety profile of osimertinib after definitive chemoradiotherapy was manageable, with no new safety concerns identified. Dose interruptions due to adverse events exerted a limited effect on exposure. The majority of radiation pneumonitis were mild to moderate, with most patients able to continue or restart treatment without recurrence. Taken together with the efficacy data, these safety data support the use of osimertinib administered post-definitive chemoradiotherapy for patients with unresectable stage III EGFRm NSCLC.

Reference

Kato T, et al. Osimertinib after definitive CRT in unresectable stage III EGFRm NSCLC: Safety outcomes from the Phase 3 LAURA study. Presented at WCLC 2024; Abstract OA12.03.