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Randomized Controlled Trial
. 2024 Jun;130(12):1921-1928.
doi: 10.1038/s41416-024-02696-6. Epub 2024 Apr 25.

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

Anne Hansen Ree  1   2 , Jūratė Šaltytė Benth  3   4 , Hanne M Hamre  5 , Christian Kersten  5   6 , Eva Hofsli  7   8 , Marianne G Guren  3   9 , Halfdan Sorbye  10   11 , Christin Johansen  5 , Anne Negård  3   12 , Tonje Bjørnetrø  5 , Hilde L Nilsen  3   13 , Jens P Berg  3   14 , Kjersti Flatmark  3   15   16 , Sebastian Meltzer  5
Affiliations
Randomized Controlled Trial

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

Anne Hansen Ree et al. Br J Cancer. 2024 Jun.

Abstract

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).

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Conflict of interest statement

AHR reports receiving research support from Bristol-Myers Squibb (on behalf of Akershus University Hospital) and a personal honorarium from MSD. HMH reports receiving personal honoraria from Bayer and Roche and serving on advisory boards of AstraZeneca, Eisai and InCyte. CK reports serving on advisory boards of AstraZeneca and Roche. HS reports receiving personal honoraria from Ipsen, Pierre Fabre and SAM Nordic and serving on advisory boards of Bayer, Hutchison MediPharma, ITM and AAA Pharma. SM reports serving on advisory board of GSK. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Kaplan–Meier curves of progression-free survival for the intention-to-treat population.
The 76 cases were stratified by (a) study arm or (b) study arm and age; <60 years: p = 0.14, ≥60 years: p = 0.052 (log-rank test).
Fig. 2
Fig. 2. Duration of study participation and efficacy assessment for the per-protocol population of 67 cases.
Objective response: Patient achieved partial or complete response according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and the consensus guidelines for assessment of response to immune-modulating therapies (iRECIST).
See this image and copyright information in PMC

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