Cesare Gridelli and Paolo Maione, Azienda Ospedaliera (AO) San Giuseppe Moscati, Avellino; Alessandro Morabito, Raffaele Costanzo, Gaetano Rocco, Gennaro Daniele, Maria Carmela Piccirillo, and Francesco Perrone, Istituto Nazionale Tumori, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) -Fondazione G. Pascale; Fortunato Ciardiello, Simona Signoriello and Ciro Gallo, Università degli Studi della Campania Luigi Vanvitelli; Roberto Bianco, Università degli Studi di Napoli Federico II; Ferdinando Riccardi, Azienda Ospedaliera di Rilievo Nazionale Cardarelli, Naples; Luigi Cavanna, Ospedale di Piacenza, Piacenza; Andrea Luciani, Ospedale S. Paolo; Virginio Filipazzi, Ospedale L. Sacco, Polo Universitario, Milan; Andrea Luciani and Silvana Leo, Gruppo Italiano di Oncologia Geriatrica; Manlio Mencoboni, Ospedale Villa Scassi, Azienda Sanitaria Locale 3 Genovese, Genoa; Laura Bonanno, Istituto Oncologico Veneto, IRCCS, Padova; Silvana Leo, AO Vito Fazzi, Lecce; Saverio Cinieri, Ospedale Senatore Antonio Perrino, Brindisi; Marco Angelo Burgio, Istituto Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola; Domenico Bilancia, AO San Carlo, Potenza; Diego Cortinovis, Ospedale San Gerardo, Monza; Francesco Rosetti, Mirano Unità Locale Socio Sanitaria 3, Serenissima Regione Veneto, Mirano; Vittorio Gebbia, Casa di Cura La Maddalena Università di Palermo, Palermo; Fabrizio Artioli, Ospedale Ramazzini di Carpi e Ospedale di Mirandola, Carpi; Roberto Bordonaro, AO Garibaldi Nesima, Catania; Vittorio Fregoni, Istituti Clinici Scientifici Maugeri, Pavia; Fabrizio Nelli, Ospedale Belcolle, Viterbo; and Giuditta di Isernia, Ospedale S. Giovanni Calibita Fatebenefratelli, Rome, Italy.
J Clin Oncol. 2018 Sep 1;36(25):2585-2592. doi: 10.1200/JCO.2017.76.8390. Epub 2018 Jul 20.
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.
目的 在两项平行的 III 期临床试验 MILES-3 和 MILES-4 的联合分析中，测试顺铂联合一线治疗方案用于治疗老年晚期非小细胞肺癌（NSCLC）患者的疗效。
方法 将年龄超过 70 岁且东部肿瘤协作组体能状态为 0-1 的晚期 NSCLC 患者随机分配至吉西他滨或培美曲塞组，且分为无顺铂组和有顺铂组。每个试验要求 382 例事件发生，以检测死亡风险比（HR）为 0.75，检验效能为 80%，双侧α值为.05。由于入组速度较慢，试验提前关闭，但联合数据库允许我们根据意向治疗和试验、组织类型、非铂类伴随药物、分期、体能状态、性别、年龄和研究中心规模进行调整，来分析顺铂的疗效。
结果 从 2011 年 3 月至 2016 年 8 月，531 例患者（MILES-3，299 例；MILES-4，232 例）被分配至无顺铂的吉西他滨或培美曲塞组（n = 268）或有顺铂的吉西他滨或培美曲塞组（n = 263）。中位年龄为 75 岁，79%为男性，70%为非鳞癌组织学类型。中位 2 年随访期间，记录到 384 例死亡和 448 例无进展生存事件。顺铂组的总生存时间未显著延长（HR，0.86；95%CI，0.70 至 1.05；P =.14），且全球健康状况评分的生活质量未得到改善，而无进展生存时间（HR，0.76；95%CI，0.63 至 0.92；P =.005）和客观缓解率（15.5%比 8.5%；P =.02）显著改善。顺铂组更易发生严重的血液学毒性、乏力和厌食。
结论 对于老年晚期 NSCLC 患者，顺铂联合单药化疗不能显著延长总生存时间，也不能改善全球健康状况评分的生活质量。
