Osimertinib after definitive CRT in unresectable stage III EGFR-mutated NSCLC: safety outcomes from the phase 3 LAURA study

In the multinational phase 3 LAURA study, osimertinib demonstrated a significant progression-free survival benefit versus placebo after definitive chemoradiotherapy (CRT) in unresectable stage III EGFR-mutated non-small cell lung cancer (NSCLC). In-depth safety data from LAURA have now been published. Patients without progression after definive CRT were randomized 2:1 to receive osimertinib (n=143) or placebo (n=73). Median exposure was 24.0 months in the osimertinib group and 8.3 months in the placebo group. 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. Exposure-adjusted rates of grade ≥3 AEs and serious AEs were 18 versus 13 and 20 versus 15 per 100 patient-years with osimertinib versus placebo, respectively; AEs led to treatment interruption in 56% versus 25.0% and to discontinuation in 13% versus 5%. Radiation pneumonitis events were numerically higher in the osimertinib group versus the placebo group (48% versus 38%) but were mostly low grade; almost all events were reported by week 18 post randomization. Interstitial lung disease was mainly grade 1-2 and manageable; most events occurred within 20 weeks post-randomization. The authors conclude that osimertinib after definitive CRT had an acceptable and manageable safety/tolerability profile, with no new safety findings.