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Abstract：
BACKGROUND: The randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines.
METHODS: Patients with CRC in the Optum\'s de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group.
RESULTS: 703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% (n = 66/310) to 45% (n = 178/393), the proportion who received standard dosing decreased from 79% (n = 244/310) to 55% (n = 215/393), the proportion who initiated their third treatment cycle increased from 36% (n = 113/310) to 46% (n = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1).
CONCLUSIONS: Following inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib.
METHODS: Patients with CRC in the Optum\'s de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group.
RESULTS: 703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% (n = 66/310) to 45% (n = 178/393), the proportion who received standard dosing decreased from 79% (n = 244/310) to 55% (n = 215/393), the proportion who initiated their third treatment cycle increased from 36% (n = 113/310) to 46% (n = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1).
CONCLUSIONS: Following inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib.
摘要：
背景：随机，剂量优化，美国转移性结直肠癌(CRC)患者的开放标签ReDOS研究表明，与标准给药方法相比，以80mg/d的剂量服用瑞戈非尼,并根据耐受性逐步升级至160mg/d,可增加达到第三个治疗周期的患者比例,并降低不良事件发生率,同时不影响疗效.随后，美国国家综合癌症网络(NCCN)临床实践指南将ReDOS剂量递增策略作为瑞戈非尼的替代给药方案纳入其中.使用美国索赔数据库进行回顾性分析，以评估在NCCN指南中纳入该剂量递增策略是否影响了美国常规临床实践中灵活给药的使用。并在NCCN指南中描述纳入前后的临床结果。
方法：在2016年1月至2020年6月期间，Optum取消识别的Clinformatics®DataMart数据库中首次启动regorafenib的CRC患者根据是否在NCCN指南中纳入ReDOS之前或之后启动regorafenib进行分层。两组：灵活给药（<160mg/天；第一个治疗周期<84片）和标准给药（160mg/天；第一个治疗周期≥84片）。主要终点是开始第三个治疗周期的患者比例和每组平均治疗周期数。
结果：703名患者在研究期间开始使用瑞戈非尼，其中310（44％）在将ReDOS纳入NCCN指南之前启动，393（56％）在将ReDOS纳入NCCN指南之后启动。纳入准则后，接受灵活给药的患者比例从21％（n=66/310）增加到45％（n=178/393），接受标准剂量的比例从79％（n=244/310）下降到55％（n=215/393），开始第三个治疗周期的比例从36%(n=113/310)增加到46%(n=179/393),治疗周期的平均值（标准差）从2.6（2.9）增加到3.2（3.1）。
结论：在将ReDOS纳入NCCN指南后，现实世界的数据表明，美国临床医生在临床实践中显著增加了灵活给药的使用，对于接受瑞戈非尼治疗的转移性CRC患者,潜在的临床获益和安全性结局最大化.
方法：在2016年1月至2020年6月期间，Optum取消识别的Clinformatics®DataMart数据库中首次启动regorafenib的CRC患者根据是否在NCCN指南中纳入ReDOS之前或之后启动regorafenib进行分层。两组：灵活给药（<160mg/天；第一个治疗周期<84片）和标准给药（160mg/天；第一个治疗周期≥84片）。主要终点是开始第三个治疗周期的患者比例和每组平均治疗周期数。
结果：703名患者在研究期间开始使用瑞戈非尼，其中310（44％）在将ReDOS纳入NCCN指南之前启动，393（56％）在将ReDOS纳入NCCN指南之后启动。纳入准则后，接受灵活给药的患者比例从21％（n=66/310）增加到45％（n=178/393），接受标准剂量的比例从79％（n=244/310）下降到55％（n=215/393），开始第三个治疗周期的比例从36%(n=113/310)增加到46%(n=179/393),治疗周期的平均值（标准差）从2.6（2.9）增加到3.2（3.1）。
结论：在将ReDOS纳入NCCN指南后，现实世界的数据表明，美国临床医生在临床实践中显著增加了灵活给药的使用，对于接受瑞戈非尼治疗的转移性CRC患者,潜在的临床获益和安全性结局最大化.
