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Background: The first-line treatments in metastatic colorectal cancer were FOLFOX, CAPOX, FOLFIRI and even FOLFOXIRI as basic chemotherapy regimen combined with targeted therapy. XELIRI regimen was not recommended because of the concerns about the toxicity, efficacy and controversy in optimal dosage. An increasing number of studies indicated promising efficacy with manageable safety profile of dosage and administration-adjusted XELIRI regimen. Therefore, the present study investigated the efficacy, safety and appropriate dosage of mXELIRI regimen in the first-line treatment of advanced colorectal cancer. Methods: The EXIST study was a multicenter, randomized controlled, non-inferiority study and we performed stratification based on the tumor location (left or right side). In the mXELIRI+Bev group, patients received intravenous infusion of irinotecan (a reduced dosage,150mg/m²) with bevacizumab (5mg/kg) on day 1 and oral administration of capecitabine (2000mg/m²/day) tablet on day 1-10/Q14 days. Patients in FOLFIRI+Bev group received intravenous infusion of irinotecan (180mg/m²), calcium folinate (400mg/m²) and 5-Fu (400mg/m²) bolus with bevacizumab (5mg/kg) on day 1 followed by a 46-hour continuous infusion of 5-Fu (2400mg/m²)/Q14 days. The primary endpoint was progression-free survival rate at 12 month(PFSR_12m) and the secondary endpoints included ORR,OS and safety. Results: 142 patients were enrolled and randomly assigned to receive mXELIRI+Bev (n=76) or FOLIRI+Bev (n=66) in our center between May 2018 and April 2021. Baseline characteristics were well balanced between two groups. In the mXELIRI+Bev group, 70 patients were evaluable with an ORR of 60.0% (1 complete response, CR; 41 partial response, PR; 24 stable disease, SD; 4 progression disease PD). While 57 patients were evaluable in the FOLFIRI+Bev group, with an ORR of 63.2% (36 PR; 15 SD; 6 PD). The PFSR_12m for two groups were 32.3% and 21.3%, the median PFS were 9.72 months and 8.77 months, respectively. For safety profiles, no statistical differences were observed in adverse events, such as nausea, vomiting, diarrhea, bone marrow suppression and abnormal liver function. While 10 serious adverse events were recorded in the mXELIRI+Bev group, including intestinal obstruction occurred in 8 patients, intestinal perforation occurred in 1 patients and venous thrombosis occurred in 1 patient. In the FOLIRI+Bev group, intestinal obstruction, venous thrombosis and pulmonary thrombosis was reported in one patient respectively. Conclusions: The modified biweekly XELIRI plus bevacizumab regimen demonstrated promising effect and could be well tolerated based on the data from a single center. Clinical trial information: NCT04247984.

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背景：转移性结直肠癌的一线治疗以FOLFOX、CAPOX、FOLFIRI甚至FOLFOXIRI作为基础化疗方案联合靶向治疗。不推荐 XELIRI 方案，因为担心最佳剂量的毒性、疗效和争议。越来越多的研究表明，剂量和给药调整的 XELIRI 方案的安全性可控，具有良好的疗效。因此，本研究探讨了mXELIRI方案在晚期结直肠癌一线治疗中的疗效、安全性和适宜剂量。方法：EXIST 研究是一项多中心、随机对照、非劣效性研究，我们根据肿瘤位置（左侧或右侧）进行分层。在 mXELIRI+Bev 组中，患者在第 1 天静脉输注伊立替康（减少剂量，150mg/m ²）和贝伐单抗（5mg/kg），并在第 1 天口服卡培他滨（2000mg/m ² /天）片剂-10/Q14 天。FOLFIRI+Bev 组患者在第 1 天静脉输注伊立替康 (180mg/m ² )、亚叶酸钙 (400mg/m ² ) 和 5-Fu (400mg/m ² ) 与贝伐单抗 (5mg/kg) 46 小时连续输注 5-Fu (2400mg/m ²)/Q14 天。主要终点为12个月无进展生存率（PFSR _12m），次要终点包括ORR、OS和安全性。结果： 2018 年 5 月至 2021 年 4 月期间，142 名患者被纳入并随机分配在我们中心接受 mXELI+Bev（n=76）或 FOLIRI+Bev（n=66）治疗。两组的基线特征平衡良好。在 mXELIRI+Bev 组中，70 例患者可评估，ORR 为 60.0%（1 例完全缓解，CR；41 例部分缓解，PR；24 例疾病稳定，SD；4 例疾病进展 PD）。FOLFIRI+Bev 组有 57 名患者可评估，ORR 为 63.2%（36 PR；15 SD；6 PD）。PFSR _12m两组分别为 32.3% 和 21.3%，中位 PFS 分别为 9.72 个月和 8.77 个月。对于安全性，在恶心、呕吐、腹泻、骨髓抑制和肝功能异常等不良事件中未观察到统计学差异。mXELIRI+Bev组共发生10起严重不良事件，其中肠梗阻8例，肠穿孔1例，静脉血栓形成1例。在 FOLIRI+Bev 组中，分别有 1 名患者报告了肠梗阻、静脉血栓形成和肺血栓形成。结论：根据来自单个中心的数据，改良的双周 XELIRI 加贝伐单抗方案显示出有希望的效果，并且可以很好地耐受。临床试验资料：NCT04247984。