Abstract 10P
Background
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.
Methods
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.
Results
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%).
Conclusions
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.
Clinical trial identification
NCT04035486.
Editorial acknowledgement
The authors would like to acknowledge Rachel Gater, PhD, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
C.K.K. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Takeda, Pfizer, Novartis, GSK, Merck KGA, Roche, Janssen, MSD; Financial Interests, Personal, Research Grant: AstraZeneca, Amgen, Roche, Merck KGA. D. Planchard: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Janssen, Pfizer, Roche, Pierre Fabre, Takeda, ArriVent, Mirati, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Merck, Novartis, Janssen, Pfizer, Roche, Pierre Fabre, Takeda, ArriVent, Mirati, Seagen; Non-Financial Interests, Personal, Other, Co-ordinating PI: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, AbbVie, Janssen, Pierre Fabre, Takeda, ArriVent, Mirati, Seagen. C. Ruscanu, S. Taggart, M. Albayaty: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. D. Kulkarni: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. All other authors have declared no conflicts of interest.