呼吸器ドクターNのmy Pick
論文No2739
Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050)
Ying Cheng,Tony S. Mok,Xiangdong Zhou,...Fanfan Zhu,Keith D. Wilner,Yi-Long Wu
LUNG CANCER, VOLUME 154, P176-185, APRIL 01, 2021
＜目的＞
ダコミチニブ vs ゲフィチニブをEGFR変異陽性の進行NSCLCのアジア人患者で比較する
ARCHER 1050試験の有効性、安全性を検討する。
＜方法＞
この現在進行中のランダム化オープンラベル第３相試験(NCT01774721)で新規診断された
進行EGFR陽性NSCLC適格患者を、ランダムに１：１で経口ダコミチニブ45mg/日あるいは
経口ゲフィチニブ250mg/日に割り付けた。
中央コンピューターシステムで、人種、EGFR変異タイプ（exon 19欠失／exon 21 L858R）に応じてランダム化した。
主要なエンドポイントは独立した評価者によるPFS評価である。
＜結果＞
346名のアジア人患者のうち、170名がダコミチニブに、176名がゲフィチニブに割り付けられた。
ダコミチニブのゲフィチニブに対するPFSのハザード比は
0.509(95% CI: 0.391-0.662; 1-sided p<0.0001;
median 16.5か月[95% CI: 12.9-18.3] vs 9.3か月[95% CI: 9.2-11.0])であった。
OSのハザード比は0.759(95 % CI: 0.578–0.996;
median 37.7 months [95 % CI: 30.2–44.7] vs. 29.1 months [95 % CI: 25.6–36.0])であった。
OSのベネフィットはダコミチニブを30mgから15mgに漸減しても維持されていた。
最も多い有害事象(AEs)はダコミチニブでは下痢(154[90.6%])、爪囲炎(110 [64.7 %])、
ざ瘡様皮疹(96 [56.5 %]), 口内炎(87 [51.2 %])であり、
ゲフィチニブでは下痢(100 [56.8 %]), ALT増加 (81 [46.0 %]), AST増加 (75 [42.6 %]) であった。
治療関連の重度AEsはダコミチニブで16名(9.4%)、ゲフィチニブで8名(4.5%)に認められた。
＜感想＞
EGFR変異陽性の進行非小細胞肺がんのアジア人集団において、一次治療のダコミチニブはゲフィチニブよりもPFS、OSの改善を認めたようです（ARCHER 1050)。ダコミチニブの有害事象は消化器、皮膚障害が多かったようです。
Objectives
To compare efficacy and safety of dacomitinib versus gefitinib as first-line therapy for EGFR mutation-positive advanced NSCLC in Asian patients enrolled in the ongoing ARCHER 1050 trial.
Materials and methods
In this ongoing, randomized, open-label, phase 3 trial (NCT01774721), eligible patients with newly diagnosed advanced EGFR mutation-positive NSCLC were randomized (1:1) to receive oral dacomitinib 45 mg/day or oral gefitinib 250 mg/day. Randomization, by a central computer system, was stratified by race and EGFR mutation type (exon 19 deletion mutation/exon 21 L858R substitution mutation). The primary endpoint was PFS by blinded independent review.
Results
Of 346 Asian patients, 170 were randomized to dacomitinib and 176 to gefitinib. The hazard ratio (HR) for PFS with dacomitinib versus gefitinib was 0.509 (95 % confidence interval [CI]: 0.391–0.662; 1-sided p < 0.0001; median 16.5 months [95 % CI: 12.9–18.4] vs. 9.3 months [95 % CI: 9.2–11.0]). HR for OS with dacomitinib versus gefitinib was 0.759 (95 % CI: 0.578–0.996; median 37.7 months [95 % CI: 30.2–44.7] vs. 29.1 months [95 % CI: 25.6–36.0]). The OS benefit was still maintained in those patients who had a stepwise dose reduction of dacomitinib (to 30 and 15 mg/day). The most common adverse events (AEs) were diarrhea (154 [90.6 %] patients), paronychia (110 [64.7 %]), dermatitis acneiform (96 [56.5 %]), and stomatitis (87 [51.2 %]) with dacomitinib, and diarrhea (100 [56.8 %]), alanine aminotransferase increased (81 [46.0 %]), and aspartate aminotransferase increased (75 [42.6 %]) with gefitinib. Treatment-related serious AEs were reported in 16 (9.4 %) and 8 (4.5 %) patients treated with dacomitinib and gefitinib, respectively.
Conclusion
First-line dacomitinib was associated with significant prolongation of PFS and improved OS compared with gefitinib in Asian patients with EGFR mutation-positive advanced NSCLC. The AE profiles of dacomitinib and gefitinib in Asian patients were consistent with the overall ARCHER 1050 population.