Shin Ji Eun, Lim Sung Hee, Lee Jeeyun, Lim Ho Yeong, Park Young Suk, Kim Seung Tae
Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Front Oncol. 2024 Sep 30;14:1450732. doi: 10.3389/fonc.2024.1450732. eCollection 2024.
Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer.
This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens.
In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, =0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib.
The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.
TAS-102（曲氟尿苷/替匹嘧啶）联合或不联合贝伐单抗的两种治疗方案均被视为难治性转移性结直肠癌患者挽救治疗的标准选择。
本分析纳入了2022年7月至2023年11月期间在三星医疗中心接受TAS-102联合贝伐单抗或单独使用TAS-102治疗的转移性结直肠癌患者。我们评估了两种治疗方案的客观缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和安全性。
本分析共纳入139例患者。中位年龄为60.8岁，既往治疗线数的中位数为4（范围：2.45 - 6.55）。超过一半的受试者（56.8%）有RAS突变，92.9%接受过既往抗VEGF治疗。83例（59.7%）患者接受了TAS-102与贝伐单抗的联合治疗，56例（40.3%）患者单独接受TAS-102治疗。在TAS-102联合贝伐单抗组中，既往接受过瑞戈非尼治疗的患者有14例，单独使用TAS-102组有5例。联合治疗组的疾病控制率为51.8%，单独使用TAS-102组为32.1%。联合治疗组的中位PFS为3.3个月（95%CI，2.7 - 6.6），单独使用TAS-102组为2.5个月（95%CI，2.0 - 3.8）（HR，0.56；95%CI，0.38 - 0.82；p = 0.003）。这两组的中位OS分别为10.8个月（95%CI，8.4 - NA）和6.0个月（95%CI，4.8 - 9.8）（HR，0.62；95%CI，0.40 - 0.97，p = 0.033）。在TAS-102 + 贝伐单抗组的探索性分析中，KRAS G12突变患者的OS低于无该突变的患者（HR，2.01，95%CI，1.04 - 3.90，p = 0.035）。常见的不良事件与血液学相关，包括中性粒细胞减少、贫血和血小板减少，以及恶心。虽然两组中任何级别的中性粒细胞减少发生率相似（57.8%和57.1%），但联合治疗组3级或更高级别中性粒细胞减少的发生率高于单独使用TAS-102组（31.3%对17.9%）。在治疗失败后接受后续抗癌治疗的患者中，74.1%接受了瑞戈非尼治疗。
与既往研究一致，TAS-102与贝伐单抗联合治疗的生存结果优于TAS-102单药治疗。本分析支持在临床实践中使用TAS-102与贝伐单抗联合治疗作为难治性转移性结直肠癌患者的最佳治疗选择。
