10P Safety and tolerability of first-line (1L) osimertinib (osi) ± platinum-pemetrexed in EGFRm advanced NSCLC: Data from FLAURA2

In FLAURA2 (NCT04035486) 1L osi with addition of platinum-pemetrexed chemotherapy (osi+CTx) showed significant PFS benefit vs osi alone (HR 0.62 [95% CI 0.49, 0.79] p<0.0001, per investigator) in EGFRm advanced NSCLC. Higher ≥Grade 3 (G3) AE rates were seen with osi+CTx vs osi, driven by well-recognised CTx-related AEs. We report additional safety analyses of specific AEs of interest from FLAURA2. Eligible pts (≥18 years with EGFRm advanced NSCLC, no prior tx for advanced NSCLC; stable CNS metastases allowed) were randomised 1:1 to osi+CTx (osi once daily [QD] + pemetrexed and cisplatin or carboplatin for 4 cycles every 3 weeks (Q3W) [induction], followed by osi QD + pemetrexed Q3W [maintenance]) or osi alone until disease progression/unacceptable toxicity/other discontinuation criteria. Safety was assessed via AE reporting (until 28 days after tx discontinuation) and clinical investigations. Data cutoff: 03 Apr 2023. The safety analysis set included pts who received ≥1 dose of study tx: osi+CTx n=276; osi n=275. In the osi+CTx arm, median duration of exposure was: osi 22.3, platinum CTx 2.8 and pemetrexed 8.3 months (mos). AE onset frequency and severity (osi+CTx arm) were highest during the induction period (∼0–<3 mos) and reduced over time during the maintenance period (>3 mos); ≥G3 AEs (64% overall for osi+CTx arm) reduced by approximately half from 49% (during 0–<3 mos) to 24% (during 3–‍<9 mos), and remained around this level for the rest of the tx period. The majority of ≥G3 AEs (osi+CTx arm) were haematological toxicities (neutropenia and anaemia), as expected from CTx-related AEs. AEs leading to osi discontinuation in the osi+CTx arm vs osi arm were 11% vs 6%; the most frequently reported events leading to discontinuation of osi in both arms were primarily those which mandated tx discontinuation by protocol, ILD (2% vs 2%) and pneumonitis (1% vs <1%). As expected, AE onset frequency and severity (osi+CTx arm) were highest during induction with clear reductions over time in the maintenance period. The addition of CTx had minimal impact on osi discontinuations. In FLAURA2, osi+CTx safety was consistent with the established profiles of osi and CTx, and manageable with standard medical practice.