Shitara Kohei, Doi Toshihiko, Hosaka Hisashi, Thuss-Patience Peter, Santoro Armando, Longo Federico, Ozyilkan Ozgur, Cicin Irfan, Park David, Zaanan Aziz, Pericay Carles, Özgüroğlu Mustafa, Alsina Maria, Makris Lukas, Benhadji Karim A, Ilson David H
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa-shi, Chiba, 277-8577, Japan.
Department of Gastroenterology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan.
Gastric Cancer. 2022 May;25(3):586-597. doi: 10.1007/s10120-021-01271-9. Epub 2022 Jan 8.
Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age.
In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years.
Among 507 randomized patients (n = 337 FTD/TPI; n = 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51-0.89), 0.73 (95% CI 0.52-1.02), and 0.67 (95% CI 0.33-1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients [40% (≥ 65 and ≥ 75 years); 29% (< 65 years)]; AE-related discontinuation rates did not increase with age [14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years)].
The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.
在随机、安慰剂对照的3期TAGS研究中，与安慰剂相比，曲氟尿苷和替匹嘧啶（FTD/TPI）在既往接受过治疗的转移性胃癌/胃食管交界癌（mGC/GEJC）患者中显示出生存获益且安全性可控。TAGS的这项亚组分析按年龄检查了疗效/安全性结果。
在TAGS研究中，mGC/GEJC且既往接受过≥2种治疗的患者被随机分组（2:1），接受35mg/m的FTD/TPI或安慰剂，加最佳支持治疗。进行了一项预先计划的亚组分析，以评估年龄<65岁、≥65岁和≥75岁患者的疗效和安全性结果。
在507例随机分组的患者中（n = 337例FTD/TPI；n = 170例安慰剂），年龄<65岁、≥65岁和≥75岁的患者分别占55%、45%和14%。FTD/TPI与安慰剂相比的总生存风险比在年龄<65岁、≥65岁和≥75岁的患者中分别为0.67（95%CI 0.51 - 0.89）、0.73（95%CI 0.52 - 1.02）和0.67（95%CI 0.33 - 1.37）。无论年龄如何，接受FTD/TPI治疗的患者与接受安慰剂治疗的患者相比，无进展生存期得到改善，治疗持续时间更长。在接受FTD/TPI治疗的患者中，各年龄亚组任何原因导致的≥3级不良事件（AE）发生率相似（均为80%），尽管≥3级中性粒细胞减少症在老年患者中更常见[40%（≥65岁和≥75岁）；29%（<65岁）]；AE相关的停药率并未随年龄增加[14%（<65岁），12%（≥65岁），12%（≥75岁）]。
这项亚组分析结果表明，对于接受过2种或更多先前治疗的mGC/GEJC患者，无论年龄大小，FTD/TPI治疗均具有疗效和耐受性。
