培美曲塞对比多西他赛治疗既往化疗的非小细胞肺癌的随机 III 期临床试验。

Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy.

机构信息

From Indiana University and the Hoosier Oncology Group; Eli Lilly and Company, Indianapolis, IN; The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of Colorado Cancer Center, Denver, CO; Virginia Cancer Institute, Richmond, VA; Princess Margaret Hospital and the University of Toronto, Toronto, Ontario, Canada; Instituto Arnaldo Vieira de Carvalho, Sao Paolo, Brazil; San Camillo-Forlanini Hospitals, Rome, Italy; Chang Gung Memorial Hospital, Taoyuan, Taiwan; University Hospital Basel, Petersgraben Switzerland; Fachklinik München, Gauting; Hospital Grosshansdorf, Grosshansdorf; Krankenhaus Hofheim Am Taunus, Hofheim; Thoraxklinik-Heidelberg, Heidelberg, Germany; National University Hospital, Singapore; Semmelweis Medical University Diosarok, Budapest, Hungary; Centre Francois Baclesse, Caen, France; Mayo Hospital, Lahore, Pakistan.

出版信息

J Clin Oncol. 2023 May 20;41(15):2682-2690. doi: 10.1200/JCO.22.02546.

DOI:10.1200/JCO.22.02546

PMID:37196429

Abstract

PURPOSE

To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy.

PATIENTS AND METHODS

Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m intravenously (IV) day 1 with vitamin B, folic acid, and dexamethasone or docetaxel 75 mg/m IV day 1 with dexamethasone every 21 days. The primary end point was overall survival.

RESULTS

Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance = .105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months ( = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% 5.3%; < .001), febrile neutropenia (12.7% 1.9%; < .001), neutropenia with infections (3.3% 0.0%; = .004), hospitalizations for neutropenic fever (13.4% 1.5%; < .001), hospitalizations due to other drug related adverse events (10.5% 6.4%; = .092), use of granulocyte colony-stimulating factor support (19.2% 2.6%, < .001) and all grade alopecia (37.7% 6.4%; < .001) compared with patients receiving pemetrexed.

CONCLUSION

Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available.

摘要

目的

比较培美曲塞与多西他赛在先前接受过化疗的晚期非小细胞肺癌（NSCLC）患者中的疗效和毒性。

方法

符合条件的患者体力状况 0-2 分，先前接受过一种晚期 NSCLC 的一线化疗方案，且器官功能良好。患者接受培美曲塞 500mg/m2 静脉滴注（IV）第 1 天，同时给予维生素 B、叶酸和地塞米松，或多西他赛 75mg/m2 IV 第 1 天，同时给予地塞米松，每 21 天一次。主要终点为总生存期。

结果

571 例患者被随机分配。培美曲塞和多西他赛的总体缓解率分别为 9.1%和 8.8%（方差分析=0.105）。每个治疗组的中位无进展生存期为 2.9 个月，中位生存时间分别为 8.3 个月和 7.9 个月（无统计学意义）。每个治疗组的 1 年生存率分别为 29.7%。接受多西他赛治疗的患者更易发生 3 级或 4 级中性粒细胞减少症（40.2%比 5.3%；<0.001）、发热性中性粒细胞减少症（12.7%比 1.9%；<0.001）、中性粒细胞减少合并感染（3.3%比 0.0%；=0.004）、中性粒细胞减少发热的住院治疗（13.4%比 1.5%；<0.001）、因其他药物相关不良事件住院治疗（10.5%比 6.4%；=0.092）、使用粒细胞集落刺激因子支持治疗（19.2%比 2.6%；<0.001）和所有级别脱发（37.7%比 6.4%；<0.001）。