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Abstract：
BACKGROUND: Regorafenib (R) and fruquintinib (F) are the standard third-line regimens for colorectal cancer (CRC) according to the National Comprehensive Cancer Network guidelines, but both have limited efficacy. Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair (MSS/pMMR) CRC. Due to the lack of studies comparing the efficacy between F, R, F plus programmed death-1 (PD-1) inhibitor, and R plus PD-1 inhibitors (RP), it is still unclear whether the combination therapy is more effective than monotherapy.
OBJECTIVE: To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC (mCRC) patients in clinical practice.
METHODS: A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital, and 313 MSS/pMMR mCRC patients were finally included.
RESULTS: A total of 313 eligible patients were divided into F (n = 70), R (n = 67), F plus PD-1 inhibitor (FP) (n = 95) and RP (n = 81) groups. The key clinical characteristics were well balanced among the groups. The median progression-free survival (PFS) of the F, R, FP, and RP groups was 3.5 months, 3.6 months, 4.9 months, and 3.0 months, respectively. The median overall survival (OS) was 14.6 months, 15.7 months, 16.7 months, and 14.1 months. The FP regimen had an improved disease control rate (DCR) (P = 0.044) and 6-month PFS (P = 0.014) and exhibited a better trend in PFS (P = 0.057) compared with F, and it was also significantly better in PFS than RP (P = 0.030). RP did not confer a significant survival benefit; instead, the R group had a trend toward greater benefit with OS (P = 0.080) compared with RP. No significant differences were observed between the R and F groups in PFS or OS (P > 0.05).
CONCLUSIONS: FP is superior to F in achieving 6-month PFS and DCR, while RP is not better than R. FP has an improved PFS and 6-month PFS compared with RP, but F and R had similar clinical efficacy. Therefore, FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.
OBJECTIVE: To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC (mCRC) patients in clinical practice.
METHODS: A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital, and 313 MSS/pMMR mCRC patients were finally included.
RESULTS: A total of 313 eligible patients were divided into F (n = 70), R (n = 67), F plus PD-1 inhibitor (FP) (n = 95) and RP (n = 81) groups. The key clinical characteristics were well balanced among the groups. The median progression-free survival (PFS) of the F, R, FP, and RP groups was 3.5 months, 3.6 months, 4.9 months, and 3.0 months, respectively. The median overall survival (OS) was 14.6 months, 15.7 months, 16.7 months, and 14.1 months. The FP regimen had an improved disease control rate (DCR) (P = 0.044) and 6-month PFS (P = 0.014) and exhibited a better trend in PFS (P = 0.057) compared with F, and it was also significantly better in PFS than RP (P = 0.030). RP did not confer a significant survival benefit; instead, the R group had a trend toward greater benefit with OS (P = 0.080) compared with RP. No significant differences were observed between the R and F groups in PFS or OS (P > 0.05).
CONCLUSIONS: FP is superior to F in achieving 6-month PFS and DCR, while RP is not better than R. FP has an improved PFS and 6-month PFS compared with RP, but F and R had similar clinical efficacy. Therefore, FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.
摘要：
背景：根据国家综合癌症网络指南，Regorafenib（R）和fruquintinib（F）是结直肠癌（CRC）的标准三线方案，但两者的功效都有限。几项2期试验表明，R或F与免疫检查点抑制剂联合使用可以逆转免疫抑制，并对微卫星稳定或有效的错配修复（MSS/pMMR）CRC取得有希望的疗效。由于缺乏比较F，R,F+程序性死亡-1（PD-1）抑制剂，和R加PD-1抑制剂（RP），目前尚不清楚联合治疗是否比单药治疗更有效.
目的：为临床选择MSS/pMMR转移性CRC(mCRC)患者的药物提供重要证据。
方法：2018年1月至2022年9月我院共纳入2639例CRC患者，最终纳入313例MSS/pMMRmCRC患者。
结果：总共313名符合条件的患者被分为F（n=70），R（n=67），F+PD-1抑制剂(FP)组(n=95)和RP(n=81)组。关键临床特征在各组之间平衡良好。F的中位无进展生存期（PFS），R,FP,RP组为3.5个月，3.6个月,4.9个月,和3.0个月，分别。中位总生存期(OS)为14.6个月,15.7个月，16.7个月，14.1个月。与F相比，FP方案的疾病控制率（DCR）（P=0.044）和6个月PFS（P=0.014）提高，PFS趋势更好（P=0.057）。PFS也明显优于RP(P=0.030)。RP没有赋予显著的生存益处；相反，与RP相比，R组的OS获益趋势更大（P=0.080）。R组和F组PFS和OS差异无统计学意义(P>0.05)。
结论：FP在实现6个月PFS和DCR方面优于F，虽然RP不优于R.FP与RP相比PFS和6个月PFS有所改善，但F和R的临床疗效相似。因此,FP可能是治疗MSS/pMMRmCRC的非常有前途的策略。
目的：为临床选择MSS/pMMR转移性CRC(mCRC)患者的药物提供重要证据。
方法：2018年1月至2022年9月我院共纳入2639例CRC患者，最终纳入313例MSS/pMMRmCRC患者。
结果：总共313名符合条件的患者被分为F（n=70），R（n=67），F+PD-1抑制剂(FP)组(n=95)和RP(n=81)组。关键临床特征在各组之间平衡良好。F的中位无进展生存期（PFS），R,FP,RP组为3.5个月，3.6个月,4.9个月,和3.0个月，分别。中位总生存期(OS)为14.6个月,15.7个月，16.7个月，14.1个月。与F相比，FP方案的疾病控制率（DCR）（P=0.044）和6个月PFS（P=0.014）提高，PFS趋势更好（P=0.057）。PFS也明显优于RP(P=0.030)。RP没有赋予显著的生存益处；相反，与RP相比，R组的OS获益趋势更大（P=0.080）。R组和F组PFS和OS差异无统计学意义(P>0.05)。
结论：FP在实现6个月PFS和DCR方面优于F，虽然RP不优于R.FP与RP相比PFS和6个月PFS有所改善，但F和R的临床疗效相似。因此,FP可能是治疗MSS/pMMRmCRC的非常有前途的策略。
