568P First-line (1L) osimertinib + platinum-pemetrexed in EGFR-mutated (EGFRm) advanced NSCLC: Updated FLAURA2 safety run-in (SRI) results

Osimertinib (osi), a third-generation, CNS-active EGFR-TKI, is the preferred 1L treatment for EGFRm advanced NSCLC, based on significant clinical benefit in the FLAURA study; however, most patients (pts) will develop disease progression. FLAURA2 (NCT04035486) is a global, phase III, open-label, randomised study of 1L osi + platinum-pemetrexed (pem) vs osi monotherapy in EGFRm advanced NSCLC. The FLAURA2 SRI phase assessed the safety/tolerability of the combination prior to the randomised period. We report final data following 3-years additional follow-up (previous data cut-off [DCO]: 19 Feb 2020). Overall, 30 pts (≥18 years; ≥20 years Japan) with locally advanced/metastatic NSCLC received oral osi 80 mg once daily (QD) + either intravenous cisplatin 75 mg/m2 or carboplatin AUC5 + pem 500 mg/m2 every 3 weeks (Q3W) for 4 cycles, then maintenance osi (80 mg QD) + pem 500 mg/m2 (Q3W) until progression/discontinuation. SRI primary endpoint: safety; secondary endpoints: ORR, DCR, duration/depth of response and OS. DCO: 03 Apr 2023. Median age (range): 61 (45–84) years; 63% female; 73% Asian, 37% former smoker. Median exposure (range): 38.6 (1.9–44.6) months osi / 15.0 (1.0–64.0) cycles pem; 47% ongoing osi and 17% ongoing pem at DCO; 80% completed 4 cycles carbo/cis-platin. With 3 further years’ exposure, 2 more pts had adverse events (AEs) (n=29 [97%] total), 5 more had serious AEs (n=11 [37%] total), 4 more had Grade ≥3 AEs (n=15 [50%] total) and 1 new AE leading to death (n=2 [7%] total). No new cases of ILD/pneumonitis reported. New Grade ≥3 AEs included COVID-19/pneumonia (n=1 each). New AEs leading to discontinuation: 4 pem (n=10 [33%] total); none osi. No new safety signals were observed. Clinical benefit was observed (Table). Osi + platinum-pem was well tolerated and clinical benefit continued with 3 further years’ exposure. Data support long-term tolerability of 1L osi + platinum-pem for EGFRm advanced NSCLC.Table: 568PEfficacy endpointOsimertinib + carboplatin/cisplatin + pemetrexed (N=30)Confirmed ORR, n (%) (95% CI)Complete responsePartial response26 (87) (69.3–96.2)3 (10)23 (77)Non-response, n (%)Stable disease ≥35 days4 (13)Median duration of response, months (range)34.0 (2.0–43.0)Best percentage change from baseline in target lesion size, median % (range)-59.6 (-100.0 – -6.4)DCR, n (%) (95% CI)30 (100) (88.4–100.0)Median OS, months (95% CI)2 year OS, % (95% CI)3 year OS, % (95% CI)NR (34.0–NC)90 (72.1–96.7)69 (48.9–82.6)Median PFS, months (95% CI)2 year PFS, % (95% CI)3 year PFS, % (95% CI)NR (25.6–NC)76 (55.9–87.7)55 (35.6–71.0)CI, confidence interval; NC, not calculable; NR, not reached Open table in a new tab