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

Autor: Ree AH; Department of Oncology, Akershus University Hospital, Lørenskog, Norway. a.h.ree@medisin.uio.no.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. a.h.ree@medisin.uio.no., Šaltytė Benth J; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway., Hamre HM; Department of Oncology, Akershus University Hospital, Lørenskog, Norway., Kersten C; Department of Oncology, Akershus University Hospital, Lørenskog, Norway.; Department of Research, Sørlandet Hospital, Kristiansand, Norway., Hofsli E; Department of Oncology, St Olav's Hospital, Trondheim, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Guren MG; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Oncology, Oslo University Hospital, Oslo, Norway., Sorbye H; Department of Oncology, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway., Johansen C; Department of Oncology, Akershus University Hospital, Lørenskog, Norway., Negård A; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Radiology, Akershus University Hospital, Lørenskog, Norway., Bjørnetrø T; Department of Oncology, Akershus University Hospital, Lørenskog, Norway., Nilsen HL; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway., Berg JP; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway., Flatmark K; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Gastroenterological Surgery, Oslo University Hospital, Oslo, Norway.; Department of Tumour Biology, Oslo University Hospital, Oslo, Norway., Meltzer S; Department of Oncology, Akershus University Hospital, Lørenskog, Norway.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2024 Jun; Vol. 130 (12), pp. 1921-1928. Date of Electronic Publication: 2024 Apr 25.
DOI: 10.1038/s41416-024-02696-6
Abstrakt: 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).
(© 2024. The Author(s).)
Databáze: MEDLINE
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