COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer.

Preclinical studies in CRC and clinical data from other cancers suggest that vascular endothelial growth factor inhibition and chemotherapy can synergize with PD-L1 inhibition.

CRC的临床前研究和其他癌症的临床数据表明，血管内皮生长因子抑制和化疗可以与PD-L1抑制产生协同作用。

Methods

The NRG-GI004/SWOG-S1610 (COMMIT) three-arm prospective phase III open-label trial randomly assigned first-line dMMR/MSI-H mCRC patients (1:1:1) to either: mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m², and 46-hour infusional 5-FU 2,400 mg/m²)/bevacizumab (FFX/bev), or atezolizumab (atezo) monotherapy (840 mg IV once every 2 weeks), or the combination of FFX/bev/atezo.

NRG-GI004/SWOG-S1610（COMMIT）三项臂前瞻性III期开放标签试验随机将一线dMMR/MSI-H mCRC患者（1:1:1）分配到以下任一组：mFOLFOX6（奥沙利铂85 mg/m²，亚叶酸钙400 mg/m²，5-FU冲击剂量400 mg/m²，和46小时输注5-FU 2,400 mg/m²）/贝伐单抗（FFX/bev），或阿替利珠单抗（atezo）单药治疗（840 mg IV每两周一次），或FFX/bev/atezo的组合。

The primary end point was progression-free survival(PFS) in the intent-to-treat population.

主要终点是意向治疗人群中的无进展生存期（PFS）。

Because of KEYNOTE 177 results, the FFX/bev arm was closed after 20 patients were enrolled.

由于KEYNOTE 177的结果，FFX/bev组在招募了20名患者后被关闭。

The study continued with atezo alone versus FFX/bev/atezo, with a revised sample size of 100 patients in the two remaining arms (120 patients across all three arms).

研究继续进行阿替利珠单抗单药治疗与FFX/bev/atezo的比较，两个剩余组的样本量修订为100名患者（三个组总共120名患者）。

Results

From November 2017 to March 2025, a total of 102 patients were enrolled in the three arms: FFX/bev: n = 20, atezo: n = 41, and FFX/bev/atezo: n = 41.

从2017年11月到2025年3月，共有102名患者被纳入三个组：FFX/bev：n = 20，atezo：n = 41，FFX/bev/atezo：n = 41。

At a median follow-up of 46 months for the two arms (median age: 63.3 years; 47.6% female; 23.2% BRAF V600E mutated), PFS of FFX/bev/atezo was superior to that of atezo (hazard ratio[HR], 0.439 [95% CI, 0.23 to 0.84]; P = .0103) and below the critical value of 0.0152.

在两个组的中位随访时间为46个月（中位年龄：63.3岁；女性占47.6%；23.2%的患者为BRAF V600E突变），FFX/bev/atezo的无进展生存期优于atezo（风险比[HR]，0.439 [95% CI, 0.23至0.84]；P = .0103），且低于0.0152的临界值。

The objective response ratewas 86.1% versus 46%, and the disease control rate at 12 months was 64.7% versus 32.4% in the FFX/bev/atezo arm compared with the atezo-only arm, respectively.

客观缓解率在FFX/bev/atezo组为86.1%，而在atezo单药组为46%，12个月疾病控制率分别为64.7%和32.4%。

Grade 3 or higher adverse events of any attribution occurred in 52 patients (atezo: 18; combination arm: 34).

任何原因导致的3级或更高级别的不良事件发生在52名患者中（atezo: 18; 联合用药组: 34）。

Conclusions

The combination of FFX/bev plus atezo led to significantly longer PFS compared with atezo monotherapy in the first-line treatment of dMMR/MSI-H mCRC.

FFX/bev加atezo的联合治疗与atezo单药治疗相比，在dMMR/MSI-H mCRC的一线治疗中显著延长了无进展生存期（PFS）。