FLAURA2: Safety and CNS outcomes of first-line (1L) osimertinib (osi) chemotherapy (CTx) in EGFRm advanced NSCLC

In FLAURA2 (NCT04035486), osi, a 3rd gen CNS-active EGFR-TKI, combined with platinum-pemetrexed (osi-CTx) showed a statistically significant improvement vs osi-monotherapy (osi-mono) in PFS per investigator (HR [95% CI]: 0.62 [0.49–0.79], p<0.001) with a manageable and tolerable safety profile. Addition of CTx did not affect osi exposure. 76% of pts completed 4 CTx cycles; median duration of pemetrexed exposure was 8.3 mos. 40% of FLAURA2 pts had baseline CNS metastases (mets); we report exploratory analyses of CNS efficacy by CNS blinded independent central review (BICR; conducted by neuroradiologist). Updated safety data will be reported. Eligible pts (≥18 y [Japan: ≥20] with EGFRm advanced NSCLC, no prior tx for advanced NSCLC; asymptomatic CNS mets not requiring steroids or stable >2 wks after definitive tx/steroids were allowed) were randomised 1:1 to 1L osi-CTx or osi-mono until progression/discontinuation. Brain imaging (MRI preferred) was performed in all pts at baseline + progression, and at scheduled assessments until progression for pts with baseline CNS mets. CNS endpoints (modified RECIST1.1) included CNS PFS, CNS response and CNS DoR by CNS BICR. Safety was assessed by CTCAE v5. Data cutoff: 3 Apr 2023. Of 557 pts randomised, 118/279 (osi-CTx) and 104/278 (osi-mono) were included in the CNS BICR full analysis set (cFAS; pts with ≥1 measurable and/or non-measurable lesion); 40/118 (osi-CTx) and 38/104 (osi-mono) were included in the CNS evaluable for response set (cEFR; pts with ≥1 measurable lesion). Demographics were balanced across tx arms. CNS efficacy is shown (Table). Safety profile was similar in the cFAS and overall population. The safety and tolerability profile during the course of tx will be described. In FLAURA2, pts with CNS mets in the osi-CTx arm had a clinically meaningful reduction in the risk of CNS progression, with high CNS ORR (and high CR) and durable responses, with a manageable and tolerable safety profile.Table: LBA68cFAScEFROsi-CTx(n=118)Osi-mono(n=104)Osi-CTx(n=40)Osi-mono(n=38)CNS ORR, n (%)86 (73)72 (69)35 (88)33 (87)- CR, n (%)70 (59)45 (43)19 (48)6 (16)Median CNS DoR, mos (95% CI)NR (23.8–NC)26.2 (19.4–NC)NR (21.6–NC)20.9 (12.6–NC)BICR CNS PFS- HR (95% CI)*0.58 (0.33–1.01)0.40 (0.19–0.84)- Median, mos (95% CI)30.2 (28.4–NC)27.6 (22.1–NC)NR (23.0–NC)17.3 (13.9–NC)*Analysed using stratified (cFAS; by race, WHO PS and EGFRm test method) or unstratified (cEFR) log-rank testCR, complete response; DoR, duration of response; NC, not calculable; NR, not reached; ORR, objective response rate; PFS, progression-free survival Open table in a new tab