Department of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom; School of Cancer and Pharmaceutical Sciences, King's College London, Guy's Hospital, London, United Kingdom.
Department of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
Clin Colorectal Cancer. 2021 Dec;20(4):342-349. doi: 10.1016/j.clcc.2021.09.009. Epub 2021 Sep 26.
The orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study.
We performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom.
A total of 236 patients were included with median age of 69 years. All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG ≥ 2. Median duration of trifluridine/tipiracil treatment was 3 months with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 and median PFS 3.3 months. A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. The most common grade 3 toxicities were neutropenia (34%), fatigue (10%), anemia (9%) and febrile neutropenia (5%). Baseline NLR <5 and CEA <200 had favorable prognostic (HR: 0.52 and 0.39, P≤ .001) and predictive value (OR: 4.1 and 6.7, P< .05). Development of grade 3 neutropenia predicted treatment response (OR: 0.32, P< .001). Following treatment with trifluridine/tipiracil 41% were referred for phase I trial or rechallenged with chemotherapy.
Trifluridine/tipiracil is well tolerated in refractory mCRC patients with comparable efficacy and toxicity profile to that of the phase III RECOURSE. Pretreatment NLR and CEA could serve as potential markers for patient selection, while treatment-induced grade 3 neutropenia predicted response. Prospective validation is needed.
口服三氟尿苷/替匹嘧啶联合疗法已被批准用于三线治疗 mCRC，在 III 期 RECURSE 研究中显示出生存获益和可接受的毒性特征。
我们对 2016 年至 2019 年间英国 8 家癌症中心接受三氟尿苷/替匹嘧啶治疗的 mCRC 患者进行了多中心回顾性真实世界分析。
共纳入 236 例患者，中位年龄为 69 岁。所有患者均接受过至少 2 线含氟嘧啶类化疗联合奥沙利铂或伊立替康的治疗。约 10%的患者 ECOG 评分≥2。三氟尿苷/替匹嘧啶治疗的中位持续时间为 3 个月，客观缓解率为 2.1%，疾病控制率为 21.6%。中位 OS 为 7.6 个月，中位 PFS 为 3.3 个月。27%的患者需要减少剂量，7.6%的患者因毒性而停止治疗。最常见的 3 级毒性为中性粒细胞减少（34%）、疲劳（10%）、贫血（9%）和发热性中性粒细胞减少（5%）。基线 NLR<5 和 CEA<200 具有良好的预后（HR：0.52 和 0.39，P≤0.001）和预测价值（OR：4.1 和 6.7，P<0.05）。3 级中性粒细胞减少的发生预测了治疗反应（OR：0.32，P<0.001）。接受三氟尿苷/替匹嘧啶治疗后，41%的患者被转介参加 I 期试验或接受化疗再挑战。
三氟尿苷/替匹嘧啶在难治性 mCRC 患者中耐受良好，疗效和毒性特征与 III 期 RECURSE 研究相当。治疗前 NLR 和 CEA 可作为患者选择的潜在标志物，而治疗诱导的 3 级中性粒细胞减少预测反应。需要前瞻性验证。
