論文No1829
Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials
Cesare Gridelli, Alessandro Morabito, Luigi Cavanna, Andrea Luciani, Paolo Maione, Laura Bonanno, Virginio Filipazzi, Silvana Leo, Saverio Cinieri, Fortunato Ciardiello, Marco Angelo Burgio, Domenico Bilancia, Diego Cortinovis, Francesco Rosetti, Roberto Bianco, Vittorio Gebbia, Fabrizio Artioli, Roberto Bordonaro, Vittorio Fregoni, Manlio Mencoboni, Fabrizio Nelli, Ferdinando Riccardi, Giuditta di Isernia, Raffaele Costanzo, Gaetano Rocco, Gennaro Daniele, Simona Signoriello, Maria Carmela Piccirillo, Ciro Gallo, and Francesco Perrone
JCO, Vol36, No25, pp. 2585–2592, 2018.
＜目的＞
進行非小細胞肺がん(NSCLC)の高齢者への１次治療にシスプラチンを使用する効果を
２つの平行第３相試験、MILES-3, MILES-4の複合解析で検討する。
＜方法＞
ECOG基準でPS0-1の70歳以上齢者の進行NSCLC患者をランダムにゲムシタビンあるいはペメトレキセドに、
シスプラチンあり／なしで割り付けた。
それぞれの試験で死亡のハザード比0.75、2方向αエラー0.05を達成するのに382のイベントが必要とされた。
死亡発生率が少ないため試験は早期中止になったが、
データ統合によりITT集団において、試験、組織型、プラチナ以外の薬剤、進行度、PS、性別、年齢、
試験センターの大きさで補正してシスプラチンの効果を解析できた。
＜結果＞
2011年3月から2016年8月にかけて531名(MILES-3, 299; MILES-4, 232)を、
シスプラチンなしでゲムシタビンまたはペメトレキセド(268名)、
あるいはシスプラチンありでゲムシタビンまたはペメトレキセド(263名)に割り付けた。
中央フォローアップ期間２年で、384名の死亡、448名のPFSイベントが記録された。
OSはシスプラチン群で有意な延長を認めず(HR, 0.86; 95% CI, 0.70 to 1.05; P = .14)、
QOLの全体健康状態スコアは改善しなかった。
PFS(HR, 0.76; 95% CI, 0.63 to 0.92; P = .005)およびORR(15.5% v 8.5%; P = .02)は
シスプラチン群で有意によかった。
シスプラチン群で血液毒性、倦怠感、食欲不振はより重症だった。
＜感想＞
高齢者のNSCLC患者で１次治療でシスプラチンを追加しても、
単剤治療と比べてOSやQOLの改善は有意でなかったようです。
Purpose
To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4.
Patients and Methods
Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center.
Results
From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin.
Conclusion
The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.