CMAB009 联合伊立替康对比伊立替康单药二线治疗氟尿嘧啶和奥沙利铂失败的 KRAS 野生型转移性结直肠癌患者：一项前瞻性、开放标签、随机、III 期试验的有前途的结果。
CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients: promising findings from a prospective, open-label, randomized, phase III trial.
机构信息
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
出版信息
Cancer Commun (Lond). 2019 May 24;39(1):28. doi: 10.1186/s40880-019-0374-8.
BACKGROUND
The 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) regimen is the standard first-line treatment for metastatic colorectal cancer (mCRC), however, the optimal second-line regimen for KRAS wild-type mCRC patients is still investigational. In this study, we aimed to determine the clinical efficacy and safety of CMAB009 plus irinotecan compared to irinotecan-only as a second-line regimen for treating KRAS wild-type mCRC patients.
METHODS
Patients with KRAS wild-type mCRC who had previously failed to respond to FOLFOX treatment were randomly assigned in a 2:1 ratio, to receive CMAB009 plus irinotecan or irinotecan-only. Patients receiving irinotecan-only were permitted to switch to CMAB009 therapy on disease progression and were grouped as the sequential-CMAB009 arm. The primary endpoints were overall response rate (ORR) and median progression-free survival (PFS). The secondary endpoints were median overall survival (OS), disease control rate (DCR), clinical benefit rate (CBR), and duration of response (DOR).
RESULTS
The CMAB009 plus irinotecan arm demonstrated significantly improved ORR (33.2% vs. 12.8%; P < 0.001) and longer median PFS (169 days vs. 95 days; P < 0.001) as compared to the irinotecan-only arm. Patients receiving CMAB009 plus irinotecan also demonstrated improved DCR (80.1% vs. 65.2%, P < 0.001), CBR (30.0% vs. 14.6%, P < 0.001), and DOR (210 days vs. 109 days; P < 0.001) as compared to irinotecan-only. However, patients treated with CMAB009 had an increased risk of skin rash (66.9% vs. 5.5%, P < 0.001) and paronychia (9.8% vs. 0.0%, P < 0.001). Anti-drug antibodies (ADA) were detected in 3.6% of patients, and only 0.9% of patients who received CMAB009 experienced hypersensitivity reactions. In patients receiving sequential-CMAB009 therapy after failure with irinotecan, their median PFS was 84 days (95% CI 65 to 113 days). The median OS was 425 days for patients receiving CMAB009 plus irinotecan and 401 days for those with sequential-CMAB009 (P = 0.940).
CONCLUSIONS
Treatment with CMAB009 plus irinotecan was found to be a superior second-line regimen in comparison to irinotecan-only in KRAS wild-type mCRC patients. Further, switching to CMAB009 can be considered as an efficient third-line of treatment after treatment failure with second-line irinotecan-only. Trial registration ClinicalTrials.gov: NCT01550055, retrospectively registered on March 9, 2012.
背景
5-氟尿嘧啶/亚叶酸钙加奥沙利铂（FOLFOX）方案是转移性结直肠癌（mCRC）的标准一线治疗方案，然而，KRAS 野生型 mCRC 患者的最佳二线治疗方案仍在研究中。在这项研究中，我们旨在确定 CMAB009 联合伊立替康与单独伊立替康相比作为 KRAS 野生型 mCRC 患者二线治疗方案的临床疗效和安全性。
方法
先前对 FOLFOX 治疗无反应的 KRAS 野生型 mCRC 患者以 2:1 的比例随机分配接受 CMAB009 联合伊立替康或单独伊立替康治疗。单独接受伊立替康治疗的患者在疾病进展时允许转为 CMAB009 治疗，并被归入序贯-CMAB009 组。主要终点是总缓解率（ORR）和中位无进展生存期（PFS）。次要终点是中位总生存期（OS）、疾病控制率（DCR）、临床获益率（CBR）和缓解持续时间（DOR）。
结果
与单独接受伊立替康治疗的患者相比，CMAB009 联合伊立替康组的 ORR（33.2%比 12.8%；P<0.001）和中位 PFS（169 天比 95 天；P<0.001）均显著改善。接受 CMAB009 联合伊立替康治疗的患者也表现出改善的 DCR（80.1%比 65.2%，P<0.001）、CBR（30.0%比 14.6%，P<0.001）和 DOR（210 天比 109 天；P<0.001）与单独接受伊立替康治疗的患者相比。然而，接受 CMAB009 治疗的患者发生皮疹的风险增加（66.9%比 5.5%，P<0.001）和甲沟炎（9.8%比 0.0%，P<0.001）。在 3.6%的患者中检测到抗药物抗体（ADA），只有 0.9%接受 CMAB009 治疗的患者发生过敏反应。在伊立替康治疗失败后接受序贯-CMAB009 治疗的患者中，中位 PFS 为 84 天（95%CI 65 至 113 天）。接受 CMAB009 联合伊立替康治疗的患者中位 OS 为 425 天，而接受序贯-CMAB009 治疗的患者为 401 天（P=0.940）。
结论
与单独接受伊立替康相比，CMAB009 联合伊立替康在 KRAS 野生型 mCRC 患者中被发现是一种更好的二线治疗方案。此外，在二线伊立替康治疗失败后，转为 CMAB009 治疗可被视为一种有效的三线治疗方法。临床试验注册：ClinicalTrials.gov：NCT01550055，于 2012 年 3 月 9 日进行了回顾性注册。
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