Phase II study of anlotinib in combination with oxaliplatin and capecitabine for patients with RAS/BRAF wild-type metastatic colorectal adenocarcinoma as the first-line therapy.
Phase II study of anlotinib in combination with oxaliplatin and capecitabine for patients with RAS/BRAF wild-type metastatic colorectal adenocarcinoma as the first-line therapy.
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安罗替尼联合奥沙利铂和卡培他滨一线治疗RAS/BRAF野生型转移性结直肠腺癌的II期研究
DOI：
10.1186/s12916-022-02357-6
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发表时间：
2022-05-06
期刊：
影响因子：
9.3
通讯作者：
Ding, Kefeng
中科院分区：
文献类型：
--
作者：
Liu, Yue;Xiao, Qian;He, Jinjie;Hu, Hanguang;Du, Jinlin;Zhu, Yuping;Chen, Jiaqi;Liu, Zhuo;Wang, Jianping;Sun, Lifeng;Xu, Dong;Li, Jun;Liao, Xiujun;Wang, Jianwei;Cai, Yibo;Cai, Cheng;Jin, Zhekang;Wang, Liuhong;Yuan, Ying;Ding, Kefeng
安洛替尼是一种靶向VEGFR 1/2/3、FGFR 1-4、PDGFR a/β和c-kit的口服小分子酪氨酸激酶抑制剂，已证明在难治性转移性结直肠癌（mCRC）中可延长无进展生存期（PFS）。这项多中心、单组、II期、探索性研究旨在评价安洛替尼联合卡培他滨和奥沙利铂作为不可切除RAS/BRAF野生型mCRC一线治疗的疗效和安全性。入组了年龄18-75岁的RAS/BRAF野生型不可切除mCRC患者，既往未接受过全身治疗，ECOG体能状态≤1。合格的患者接受卡培他滨（850 mg/m2，p.o.，bid，每21天1-14天），奥沙利铂（130 mg/m2，i. v.，每21天第1天）和安洛替尼（12 mg，p.o.，qd，第1-14天，每21天一次）作为诱导治疗。6个周期治疗后，达到缓解或疾病稳定的患者接受卡培他滨和安洛替尼作为维持治疗，直至肿瘤进展。主要终点为根据RECIST（版本：1.1）的客观缓解率（ORR），次要终点为PFS、疾病控制率（DCR）、缓解持续时间（DOR）和安全性。2019年11月至2021年2月期间，入组了31例患者。1例患者因拒绝治疗而被排除。主要终点ORR为76.7%（95% CI，57.7-90.1），1例患者达到完全缓解，22例患者达到部分缓解。DCR为93.3%（95% CI，77.9-99.2）。中位随访时间为14.1个月（95% CI，9.9-18.3），中位PFS为11.3个月（95% CI，7.1-14.1），DOR为7.9个月（95% CI，5.5-12.7）。25例（83.3%）患者发生3级或4级治疗后出现的不良事件（TEAE）。未报告5级TEAE。最常见的3级或4级TEAE（>10%）为高血压（15/30; 50%）、中性粒细胞计数降低（8/30; 26.7%）和腹泻（4/30; 13.3%）。共有18例（60%）患者发生导致剂量降低、中断或延迟的TEAE。安洛替尼联合卡培他滨和奥沙利铂在mCRC的一线治疗中显示出相当大的ORR、DCR、PFS和DOR，毒性特征可控。 ClinicalTrials.gov：NCT04080843
Anlotinib, an oral small molecule tyrosine kinase inhibitor targeting VEGFR 1/2/3, FGFR 1-4, PDGFR a/β, and c-kit, had demonstrated prolonged progression-free survival (PFS) in refractory metastatic colorectal cancer (mCRC). This multicenter, single-arm, phase II, exploratory study was conducted to evaluate the efficacy and safety of anlotinib combined with capecitabine and oxaliplatin as first-line treatment for unresectable RAS/BRAF wild-type mCRC. Patients aged 18–75 with RAS/BRAF wild-type unresectable mCRC, without prior systemic treatment, and ECOG performance status ≤1 were enrolled. Eligible patients received capecitabine (850 mg/m2, p.o., bid, on day 1–14 every 21 days), oxaliplatin (130 mg/m2, i.v., on day 1 every 21 days), and anlotinib (12 mg, p.o., qd, on days 1–14 every 21 days) as induction therapy. Following 6 cycles of therapy, patients who achieved response or stable disease received capecitabine and anlotinib as maintenance therapy until tumor progression. The primary endpoint was objective response rate (ORR) according to RECIST (version: 1.1), and the secondary endpoints were PFS, disease control rate (DCR), duration of response (DOR), and safety. Between November 2019 and February 2021, 31 patients were enrolled. One patient was excluded for refusing treatment. The primary endpoint of ORR was 76.7% (95% CI, 57.7–90.1) with 1 patient achieving a complete response and 22 patients partial response. DCR was 93.3% (95% CI, 77.9–99.2). At a median follow-up of 14.1 months (95% CI, 9.9–18.3), median PFS was 11.3 months (95% CI, 7.1–14.1), and DOR was 7.9 months (95% CI, 5.5–12.7). Twenty-five (83.3%) patients experienced grade 3 or 4 treatment-emergent adverse events (TEAEs). No grade 5 TEAE was reported. The most common grade 3 or 4 TEAEs (>10%) were hypertension (15/30; 50%), neutrophil count decreased (8/30; 26.7%), and diarrhea (4/30; 13.3%). A total of 18 (60%) patients had TEAEs that resulted in dose reduction, interruptions, or delays. Anlotinib combined with capecitabine and oxaliplatin showed considerable ORR, DCR, PFS, and DOR in the first-line therapy of mCRC with manageable toxicity profiles. ClinicalTrials.gov: NCT04080843
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