对于未经治疗的转移性结直肠癌患者，在使用FOLFOXIRI/贝伐单抗之前使用曲拉西利：3期PRESERVE 1试验。
Trilaciclib prior to FOLFOXIRI/bevacizumab for patients with untreated metastatic colorectal cancer: phase 3 PRESERVE 1 trial.
作者信息
Lenz Heinz-Josef, Liu Tianshu, Chen Emerson Y, Horváth Zsolt, Bondarenko Igor, Danielewicz Iwona, Ghidini Michele, García-Alfonso Pilar, Jones Robert, Aapro Matti, Zhang Yanqiao, Wang Jufeng, Wang Wayne, Adeleye Jennifer, Beelen Andrew, Hubbard Joleen
机构信息
Department of Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, United States.
Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
出版信息
JNCI Cancer Spectr. 2025 Jan 3;9(1). doi: 10.1093/jncics/pkae116.
BACKGROUND
In metastatic colorectal cancer (mCRC), improvements in survival from combining leucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) with bevacizumab have come at the risk of increased rates of high-grade toxicities. Trilaciclib is indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients receiving standard-of-care chemotherapy for extensive-stage small cell lung cancer.
METHODS
Patients with untreated mCRC were randomly assigned 1:1 to trilaciclib (n = 164) or placebo (n = 162) prior to FOLFOXIRI/bevacizumab for up to 12 cycles (induction), followed by trilaciclib or placebo prior to fluorouracil/leucovorin/bevacizumab (maintenance). Co-primary endpoints were duration of severe (grade 4) neutropenia (DSN) in cycles 1-4 and occurrence of severe neutropenia (SN) during induction. Secondary endpoints included antitumor efficacy, survival, and safety.
RESULTS
The study met its co-primary endpoints. Administering trilaciclib prior to FOLFOXIRI/bevacizumab resulted in significant reductions in DSN in cycles 1-4 vs placebo (mean, 0.1 vs 1.3 days; P < .001) and occurrence of SN during induction (1.3% vs 19.7%; adjusted relative risk [96% CI] = 0.07 [0.0 to 0.3]; P < .001). Grade 3/4 adverse events, including neutropenia, diarrhea, and leukopenia, were less frequent with trilaciclib vs placebo (64.8% vs 73.1%). Trilaciclib was associated with fewer chemotherapy dose reductions and delays and with reduced administration of supportive therapies, compared with placebo. Objective response rate (41.6% vs 57.1%; P = .009) and median progression-free survival (10.3 vs 13.1 months; P < .001) were significantly lower with trilaciclib vs placebo.
CONCLUSIONS
Administering trilaciclib prior to FOLFOXIRI/bevacizumab protected the neutrophil lineage from the effects of chemotherapy-induced myelosuppression. However, antitumor efficacy endpoints favored placebo.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT04607668.
背景
在转移性结直肠癌（mCRC）中，亚叶酸钙/氟尿嘧啶/奥沙利铂/伊立替康（FOLFOXIRI）联合贝伐单抗改善生存率的同时，高级别毒性发生率有增加的风险。曲拉西利适用于降低接受广泛期小细胞肺癌标准护理化疗患者化疗引起的骨髓抑制发生率。
方法
未经治疗的mCRC患者在接受FOLFOXIRI/贝伐单抗治疗前，按1:1随机分配至曲拉西利组（n = 164）或安慰剂组（n = 162），进行长达12个周期的诱导治疗，随后在氟尿嘧啶/亚叶酸钙/贝伐单抗治疗前给予曲拉西利或安慰剂进行维持治疗。共同主要终点为第1 - 4周期严重（4级）中性粒细胞减少持续时间（DSN）和诱导期严重中性粒细胞减少（SN）的发生情况。次要终点包括抗肿瘤疗效、生存率和安全性。
结果
该研究达到了其共同主要终点。在FOLFOXIRI/贝伐单抗治疗前给予曲拉西利，与安慰剂相比，第1 - 4周期DSN显著缩短（平均，0.1天对1.3天；P < 0.001），诱导期SN发生率显著降低（1.3%对19.7%；校正相对风险[96%CI] = 0.07[0.0至0.3]；P < 0.001）。与安慰剂相比，曲拉西利组3/4级不良事件（包括中性粒细胞减少、腹泻和白细胞减少）的发生率更低（64.8%对73.1%）。与安慰剂相比，曲拉西利组化疗剂量减少和延迟的情况更少，支持治疗的使用也减少。曲拉西利组的客观缓解率（41.6%对57.1%；P = 0.009）和中位无进展生存期（10.3个月对13.1个月；P < 0.001）显著低于安慰剂组。
结论
在FOLFOXIRI/贝伐单抗治疗前给予曲拉西利可保护中性粒细胞系免受化疗诱导的骨髓抑制影响。然而，抗肿瘤疗效终点更倾向于安慰剂。
试验注册
ClinicalTrials.gov：NCT04607668。
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