Background

We evaluated first-line treatment of metastatic microsatellite-stable colorectal cancer with short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade.

Methods

Patients were randomly assigned to chemotherapy (the FLOX regimen; control group) or alternating two cycles each of FLOX and nivolumab (experimental group). Radiographic response assessment was done every eight weeks with progression-free survival (PFS) as the primary endpoint. Cox proportional-hazards regression models estimated associations between PFS and relevant variables. A post hoc analysis explored C-reactive protein as signal of responsiveness to immune checkpoint blockade.

Results

Eighty patients were randomised and 38 in each group received treatment. PFS was comparable—control group: median 9.2 months (95% confidence interval (CI), 6.3–12.7); experimental group: median 9.2 months (95% CI, 4.5–15.0). The adjusted Cox model revealed that experimental-group subjects aged ≥60 had significantly lowered progression risk (p = 0.021) with hazard ratio 0.17 (95% CI, 0.04–0.76). Experimental-group patients with C-reactive protein <5.0 mg/L when starting nivolumab (n = 17) reached median PFS 15.8 months (95% CI, 7.8–23.7). One-sixth of experimental-group cases (all KRAS/BRAF-mutant) achieved complete response.

Conclusions

The investigational regimen did not improve the primary outcome for the intention-to-treat population but might benefit small subgroups of patients with previously untreated, metastatic microsatellite-stable colorectal cancer.

Trial registration

ClinicalTrials.gov number, NCT03388190 (02/01/2018).

中文翻译：

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基于奥沙利铂的一线化疗和纳武单抗治疗转移性微卫星稳定结直肠癌——随机 METIMMOX 试验

背景

我们评估了基于奥沙利铂的短程化疗与免疫检查点阻断交替治疗转移性微卫星稳定结直肠癌的一线治疗。

方法

患者被随机分配接受化疗（FLOX 方案；对照组）或 FLOX 和纳武单抗各交替两个周期（实验组）。每八周进行一次放射学反应评估，以无进展生存期（PFS）作为主要终点。 Cox 比例风险回归模型估计 PFS 与相关变量之间的关联。一项事后分析探讨了 C 反应蛋白作为对免疫检查点封锁的反应信号。

结果

80 名患者被随机分配，每组 38 名接受治疗。 PFS 相当——对照组：中位 9.2 个月（95% 置信区间 (CI)，6.3–12.7）；实验组：中位时间 9.2 个月（95% CI，4.5–15.0）。调整后的 Cox 模型显示，年龄≥60 岁的实验组受试者的进展风险显着降低（p  = 0.021），风险比为 0.17（95% CI，0.04-0.76）。开始纳武单抗治疗时 C 反应蛋白 <5.0 mg/L 的实验组患者 ( n  = 17) 达到中位 PFS 15.8 个月 (95% CI, 7.8–23.7)。六分之一的实验组病例（均为KRAS/BRAF突变体）获得完全缓解。

结论

研究方案并未改善意向治疗人群的主要结局，但可能使先前未经治疗的转移性微卫星稳定结直肠癌患者的小亚群受益。

试用注册

ClinicalTrials.gov 编号，NCT03388190 (02/01/2018)。