630MO - First-line (1L) osimertinib (osi) ± platinum-pemetrexed chemotherapy (CTx) for EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC): FLAURA2 Asian cohort

Background

Osi is a 3rd-generation CNS-active EGFR-TKI. In the global, Ph III, open-label, randomised FLAURA2 study (NCT04035486) in patients (pts) with EGFRm advanced NSCLC, 1L osi + CTx demonstrated a statistically significant improvement in progression-free survival (PFS) vs osi monotherapy (mono). We report data from the Asian cohort.

Methods

Eligible pts: ≥18 (Japan ≥20) 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. Randomisation was 1:1 to osi + CTx (osi QD + pemetrexed and cisplatin/carboplatin Q3W [4 cycles; induction], then maintenance osi QD + pemetrexed Q3W) or osi mono until progression/discontinuation. Stratification was 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. Secondary endpoints included: OS, ORR, DoR and safety. Data cut-off: 3 Apr 23 (second interim OS analysis: 8 Jan 24).

Results

In the Asian cohort (osi + CTx/osi, n=169/164) baseline characteristics were: median age, 61/61 yrs; female, 62/57%; Ex19del, 53/61%; L858R, 46/38%; CNS metastases, 47/42%; median baseline tumour size, 52/50 mm. PFS was improved with osi + CTx vs osi (Table). Median duration of osi exposure with osi + CTx vs osi: 24 vs 21 mos. In the osi + CTx arm, 75% of pts received ≥4 cycles of platinum CTx. In the osi + CTx vs osi arms: grade (G) ≥3 adverse events (AEs) occurred in 67 vs 24% pts; AEs leading to osi discontinuation in 10 vs 7%; no instances of G4/5 interstitial lung disease. Table: 630MO

*DCO 3 Apr 23^†Overall^‡DCO 8 Jan 24CI, confidence interval; DCO, data cut-off; DoR, duration of response; HR, hazard ratio; INV, investigator; mos, months; NC, not calculable; ORR, objective response rate; OS, overall survival

Conclusions

In Asian pts with EGFRm advanced NSCLC from FLAURA2, 1L osi + CTx demonstrated a clinically meaningful PFS benefit vs osi mono, with a manageable safety/tolerability profile, as expected; this was consistent with global results (Planchard NEJM 2023). These data support osi + CTx as a 1L Tx option for Asian pts with EGFRm advanced NSCLC.

Clinical trial identification

NCT04035486; 25 July 2019.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Alice Walter, BSc, of Ashfield MedComms, an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J.C. Yang: Financial Interests, Personal, Advisory Board: Amgen; AstraZeneca; AbbVie; Bayer; Boehringer Ingelheim; Daiichi Sankyo Inc.; Eli Lilly; F. Hoffmann-La Roche; Gilead Sciences Inc.; Janssen Pharmaceuticals; Merck KGaA; Merck Sharp & Dohme Corporation; Novartis; Pfizer; Regeneron Pharmaceuticals; Takeda ; Financial Interests, Personal, Coordinating PI: AstraZeneca, Merck Sharp & Dohme Corporation, Dizal Pharmaceuticals; Financial Interests, Personal, Funding: Dizal Pharaceuticals AstraZeneca Takeda Oncology; Financial Interests, Personal, Local PI: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Daiichi Sankyo Inc.; Eli Lilly; F. Hoffmann-La Roche; Gilead Sciences Inc.; Janssen Pharmaceuticals; Merck KGaA; Merck Sharp & Dohme Corporation; Novartis;Takeda Oncology, Yuhan Pharmaceuticals, ArriVent, D; Financial Interests, Personal, Member: ASCO, ESMO, IASLC; Financial Interests, Personal, Research Grant: AstraZeneca; F. Hoffmann-La Roche; Financial Interests, Personal, Steering Committee Member: Amgen; AstraZeneca; Bayer; Daiichi Sankyo Inc.; Eli Lilly; Janssen Pharmaceuticals; Merck KGaA; Merck Sharp & Dohme Corporation; Takeda Oncology, Yuhan Pharmaceuticals, ArriVent, Dizal Pharmaceuticals, Black Diamond Therapeutics Inc. Numab Therapeutics AG. K. Kobayashi: Financial Interests, Personal, Research Funding: Zeria Pharmaceutical Co.; Financial Interests, Personal, Speaker, Consultant, Advisor: Daiichi Sankyo, UCB Japan; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. B. Chewaskulyong: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca. K.H. Lee: Financial Interests, Personal, Research Funding: Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Pfizer, Takeda, Eli Lilly, Yuhan, MSD, AstraZeneca. P. Feng: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Pfizer, Ono. S. Kuyama: Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, MSD, Merck, TAKEDA, ONO, Novartis, Lilly, Amgen, YUHAN, Alpha Pharmaceuticals; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, MSD, Merck, TAKEDA, ONO, Novartis, Lilly, Amgen, YUHAN. V. Sriuranpong: Financial Interests, Personal, Advisory Role: MSD, Takeda, Daiichi, Amgen, AstraZeneca; Financial Interests, Personal, Local PI: AstraZeneca, Amgen, Daiichi, MSD, Beigene; Financial Interests, Personal, Research Funding: AstraZeneca, Amgen, Daiichi, MSD, Beigene; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Takeda, AstraZeneca, Amgen, Eisai, Janssen. R.K. Li: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, ZPT Amgen, ZPT Eli Lilly, Eisai; Financial Interests, Personal, Advisory Role: BIOCON, MSD; Financial Interests, Personal, Principal Investigator: AstraZeneca, MSD, TAIHO; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, ZPT Amgen, Eli Lilly, Novartis. E. Armenteros Monterroso: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. K. Barrett: Financial Interests, Personal, Other, Paid consultant for AstraZeneca: AstraZeneca. M. Albayaty: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. All other authors have declared no conflicts of interest.