Taieb Julien, Fakih Marwan, Liposits Gabor, Prager Gerald W, Van Cutsem Eric, Ciardiello Fortunato, Amellal Nadia, Calleja Elizabeth, Liu Mei, Roby Lucas, Tabernero Josep, André Thierry
Hôpital Européen Georges-Pompidou, University Paris-Cité (Paris Descartes), SIRC CARPEM, Paris, France.
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, United States.
Front Oncol. 2025 Jan 16;14:1506075. doi: 10.3389/fonc.2024.1506075. eCollection 2024.
Trifluridine/tipiracil (FTD/TPI) is approved as monotherapy and in combination with bevacizumab for the treatment of patients with refractory metastatic colorectal cancer (mCRC). FTD/TPI plus bevacizumab showed good tolerability in the phase 3 SOLSTICE (first-line) and SUNLIGHT (later-line) trials. This pooled analysis was performed to further characterize the safety of FTD/TPI plus bevacizumab and to compare safety in untreated and previously treated patients with mCRC.
Patients must have received at least one dose of FTD/TPI plus bevacizumab in SOLSTICE (NCT03869892) or SUNLIGHT (NCT04737187). Treatment-emergent adverse events (TEAEs) in SOLSTICE and SUNLIGHT were graded per Common Terminology Criteria for Adverse Events versions 4.03 and 5.0, respectively. Times to onset/resolution of grade ≥3 hematologic TEAEs were assessed using Kaplan-Meier methodology. Treatment-related adverse events (TRAEs) were analyzed by age and Eastern Cooperative Oncology Group performance status (ECOG PS).
The pooled safety population comprised 669 patients (SOLSTICE, n = 423; and SUNLIGHT, n = 246). Grade ≥3 TEAEs were reported more frequently in SOLSTICE than in SUNLIGHT (86.8% vs. 72.4%), the most common being neutropenia and anemia. Overall, granulocyte colony-stimulating factor was used in 30.6% of patients. Median time to resolution of grade ≥3 hematologic adverse events/neutropenia to grade ≤2 was 8 days. Grade ≥3 TRAEs were more frequent in patients aged ≥75 years and those with an ECOG PS of 0 versus 1 or 2.
FTD/TPI plus bevacizumab showed a consistent and manageable safety profile across first- and later-line mCRC treatment, including in vulnerable patients. Hematologic TEAEs were mostly reversible with appropriate management.
曲氟尿苷/替匹嘧啶（FTD/TPI）已被批准作为单药疗法以及与贝伐单抗联合用于治疗难治性转移性结直肠癌（mCRC）患者。FTD/TPI联合贝伐单抗在3期SOLSTICE（一线）和SUNLIGHT（后线）试验中显示出良好的耐受性。进行这项汇总分析是为了进一步描述FTD/TPI联合贝伐单抗的安全性，并比较未接受过治疗和既往接受过治疗的mCRC患者的安全性。
患者必须在SOLSTICE（NCT03869892）或SUNLIGHT（NCT04737187）中接受过至少一剂FTD/TPI联合贝伐单抗治疗。SOLSTICE和SUNLIGHT中出现的治疗中出现的不良事件（TEAE）分别根据不良事件通用术语标准第4.03版和第5.0版进行分级。使用Kaplan-Meier方法评估≥3级血液学TEAE的发生/缓解时间。按年龄和东部肿瘤协作组体能状态（ECOG PS）分析治疗相关不良事件（TRAE）。
汇总的安全人群包括669例患者（SOLSTICE组423例；SUNLIGHT组246例）。≥3级TEAE在SOLSTICE组中的报告频率高于SUNLIGHT组（86.8%对72.4%），最常见的是中性粒细胞减少和贫血。总体而言，30.6%的患者使用了粒细胞集落刺激因子。≥3级血液学不良事件/中性粒细胞减少至≤2级的中位缓解时间为8天。≥3级TRAE在年龄≥75岁的患者以及ECOG PS为0的患者中比ECOG PS为1或2的患者更常见。
FTD/TPI联合贝伐单抗在一线和后线mCRC治疗中显示出一致且可控的安全性，包括在脆弱患者中。血液学TEAE通过适当管理大多可逆。
