Jin Ying, Li Jin, Shen Lin, Xu Jianming, Zhang Yanqiao, Zhang Jingdong, Pan Hongming, Qu Xiujuan, Chen Yamin, Zhang Qiang, Li Jinnan, Sun Miaomiao, Qin Shukui
Department of Medical Oncology, Sun Yat-Sen University Cancer Centre, Guangzhou, China.
Department of Medical Oncology, Shanghai Oriental Hospital Affiliated Tongji University East Hospital, Shanghai, China.
Front Oncol. 2022 Nov 24;12:1044328. doi: 10.3389/fonc.2022.1044328. eCollection 2022.
The objective of this study was to assess the comparative efficacy in third-line setting for metastatic CRC (mCRC) patients using matched population of FRESCO trial with fruquintinib and real-world data with other TKIs.
The arm of fruquintinib from the FRESCO phase III trial (NCT02314819) included the data of patients with metastatic CRC that progressed after at least two lines of chemotherapy and received fruquintinib treatment. An external control arm was constructed using real-world data (RWD) of patients who received other TKIs based on key eligibility criteria of FRESCO. The baseline characteristics of two arms was balanced by propensity score matching (PSM). The Kaplan-Meier method and Cox proportional hazard model was used to evaluate progression free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), respectively.
Overall, 128 patients were successfully matched by PSM in each, fruquintinib and other TKIs group. The patients in fruquintinib group showed significant increase in median PFS than other TKIs (3.71 2.49 months, HR = 0.67, 95%CI, 0.48-0.94, 0.019). In the subgroup analysis, fruquintinib showed a significant benefit in PFS compared with other TKIs among patients undergoing two or three previous chemotherapy regimens (HR 0.58, 95%CI 0.40-0.84; =0.004), with rectum as primary disease site (HR 0.52, 95%CI 0.31-0.87; =0.013), with left sided primary tumor location (HR 0.62, 95%CI 0.42-0.90; =0.011), with multiple metastasis sites (HR 0.68, 95%CI 0.48-0.97; =0.034) and with lung metastasis (HR 0.65, 95%CI 0.43-0.98; =0.042).
With the approach of establishing the external control arm from RWD, this study has demonstrated that treatment with fruquintinib significantly prolonged PFS as compared to other TKIs in patients as third-line mCRC treatment.
本研究的目的是通过将呋喹替尼的FRESCO试验的匹配人群与其他酪氨酸激酶抑制剂（TKIs）的真实世界数据进行比较，评估转移性结直肠癌（mCRC）患者三线治疗中的疗效。
FRESCO III期试验（NCT02314819）中呋喹替尼组纳入了至少接受过两线化疗后病情进展并接受呋喹替尼治疗的转移性结直肠癌患者的数据。根据FRESCO的关键纳入标准，使用接受其他TKIs治疗患者的真实世界数据（RWD）构建外部对照组。通过倾向得分匹配（PSM）使两组的基线特征达到平衡。采用Kaplan-Meier法和Cox比例风险模型分别评估无进展生存期（PFS）并估计风险比（HRs）和95%置信区间（CIs）。
总体而言，呋喹替尼组和其他TKIs组各有128例患者通过PSM成功匹配。呋喹替尼组患者的中位PFS较其他TKIs组显著延长（3.71对2.49个月，HR = 0.67，95%CI，0.48 - 0.94，P = 0.019）。在亚组分析中，与其他TKIs相比，呋喹替尼在接受过两或三线先前化疗方案的患者中（HR 0.58，95%CI 0.40 - 0.84；P = 0.004）、以直肠作为主要疾病部位的患者中（HR 0.52，95%CI 0.31 - 0.87；P = 0.013）、原发性肿瘤位于左侧的患者中（HR 0.62，95%CI 0.42 - 0.90；P = 0.011）、有多个转移部位的患者中（HR 0.68，95%CI 0.48 - 0.97；P = 0.034）以及有肺转移的患者中（HR 0.65，95%CI 0.43 - 0.98；P = 0.042），PFS均显示出显著获益。
通过从RWD建立外部对照组的方法，本研究表明，在三线mCRC治疗中，与其他TKIs相比，呋喹替尼治疗可显著延长患者的PFS。
