562P - First-line (1L) osimertinib (osi) ± platinum-pemetrexed in patients (pts) with EGFRm advanced NSCLC: FLAURA2 China cohort

Background

Osi is a third-generation, CNS active EGFR-TKI. The primary analysis of the global, phase III, open-label, randomised FLAURA2 (NCT04035486) study in pts with EGFRm advanced NSCLC demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with 1L osi + chemotherapy (osi + CT) vs osi monotherapy (osi-mono). We report data of pts in China from FLAURA2.

Methods

Eligible pts (aged ≥18 yrs with locally advanced/metastatic EGFRm [Ex19del/L858R] NSCLC, WHO PS 0/1 and no prior systemic treatment [tx] for advanced NSCLC; stable CNS metastases allowed) were randomised 1:1 to osi + CT (osi 80 mg QD + pemetrexed [pem] 500 mg/m² + either cisplatin 75 mg/m² or carboplatin AUC5 Q3W for 4 cycles, followed by osi 80 mg QD + pem 500 mg/m² Q3W) or osi-mono (80 mg QD) until progression/discontinuation criterion; stratified by race (Chinese Asian/non-Chinese Asian/non-Asian), EGFR mutation test method (local/central) and WHO PS (0/1). Primary endpoint: PFS by investigator assessment. Secondary endpoints included OS, ORR, DoR and safety. Data cut-off: 03 April 2023.

Results

Overall, 131 pts in China were randomised to osi + CT (n=67) or osi-mono (n=64). Baseline characteristics (osi + CT/osi-mono) were: median age (range), 61 (42–74)/60 (32–78) yrs; 63/59% female; 48/59% Ex19del; 51/39% L858R (1 unknown EGFR mutation type per arm); 51/42% CNS metastases. Osi + CT improved PFS vs osi-mono (49% maturity by investigator; Table). OS was immature (21% maturity); HR 0.97 (95% CI 0.45, 2.06). All grade ≥3 AEs (osi + CT/osi-mono): 75% (mainly haematological)/26%; AEs leading to osi discontinuation: 3/5%.

Conclusions

In the China cohort, osi + CT demonstrated a clinically meaningful improvement in PFS over osi-mono with a manageable safety/tolerability profile consistent with the global study population, supporting osi + platinum-pem as a new 1L tx option for pts in China with advanced EGFRm NSCLC. Table: 562P

∗In censored pts.BICR, blinded independent central review; CI, confidence interval; DoR, duration of response; HR, hazard ratio; NC, not calculable; NR, not reached; ORR, objective response rate

Clinical trial identification

FLAURA2: NCT04035486.

Editorial acknowledgement

The authors would like to acknowledge Rachel Gater, Ph.D., of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP) guidelines (https://www.ismpp.org/gpp-2022).

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

L. Jiang: Non-Financial Interests, Personal, Local PI: Shanghai Chest Hospital, Shanghai Jiao Tong University, PR China. J. Liu, Y. Liu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. D. Kulkarni, X. Huang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. P.A. Jänne: Financial Interests, Personal, Advisory Board: AstraZeneca, Mirati Therapeutics, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly and Company, Ignyte, Takeda Oncology, Novartis, Voronoi, SFJ Pharmaceuticals, Biocartis, LOXO Oncology, PUMA, Sanofi, Transcenta, Daiichi Sa; Financial Interests, Personal, Other: Dr. Jänne is a co-inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Takeda Oncology, PUMA, Astellas Pharmaceuticals, Daiichi Sankyo; Financial Interests, Personal, Royalties: Post marketing royalties from DFCI owned intellectual property on EGFR mutations licensed to Lab Corp. All other authors have declared no conflicts of interest.