First-line oxaliplatin-based chemotherapy and nivolumab for metastatic microsatellite-stable colorectal cancer-the randomised METIMMOX trial.

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).