Osimertinib after definitive CRT in unresectable stage III EGFR-mutated NSCLC: safety outcomes from the phase III LAURA study

BACKGROUND: In the phase III LAURA study, osimertinib demonstrated a statistically significant progression-free survival benefit versus placebo, and a generally tolerable safety profile, after definitive chemoradiotherapy (CRT) in unresectable stage III EGFR-mutated non-small cell lung cancer. We report in-depth safety data from LAURA. PATIENTS AND METHODS: Patients without progression during/after definitive CRT were randomized 2:1 to receive osimertinib or placebo. Safety was assessed at baseline, week 2, week 4, every 4 weeks until week 24, every 8 weeks until week 48, and every 12 weeks until study treatment discontinuation. Adverse events (AEs) of special interest included grouped terms of radiation pneumonitis (RP) and interstitial lung disease (ILD, including pneumonitis). RESULTS: Overall, 216 patients were randomized (osimertinib, 143; placebo, 73) and received ≥1 dose of study treatment; median exposure 24.0 months (osimertinib), 8.3 months (placebo). Exposure-adjusted rates of grade ≥3 AEs and serious AEs were 18 versus 13 and 20 versus 15/100 patient-years with osimertinib versus placebo, respectively. Exposure-adjusted AEs that occurred at the greatest increased frequency with osimertinib versus placebo were diarrhea and paronychia. AEs led to treatment interruption in 56 % versus 25 % of patients and to discontinuation in 13 % versus 5 % with osimertinib versus placebo, respectively. RP (grouped term) events were numerically higher in the osimertinib (48 %) versus placebo (38 %) arm but were mostly low grade; almost all events were reported by 18 weeks post-randomization. Protocol-mandated toxicity management guidelines effectively managed RP; most patients (60/69; 87 %) continued osimertinib, with or without interruption, and without recurrence (64/69; 93 %). ILD (grouped term) was mainly grade 1-2 and manageable; most events occurred within 20 weeks post-randomization. CONCLUSIONS: Osimertinib after definitive CRT had an acceptable and manageable safety/tolerability profile, with no new safety findings, supporting osimertinib as the new standard of care in this setting. LAURA clinical trial registration number: NCT03521154.