Exploratory biomarkers for oxaliplatin-induced nivolumab responsiveness in metastatic microsatellite-stable colorectal cancer

Resumo original em inglês

O que aconteceu

The randomised METIMMOX trial evaluated short-course oxaliplatin-based chemotherapy alternating with nivolumab for metastatic microsatellite-stable/mismatch repair-proficient colorectal cancer. In a post hoc analysis, we investigated whether tumour mutations or patients' systemic inflammation might provide insights into responsiveness to the METIMMOX regimen.

Patients received either oxaliplatin-based chemotherapy (control group) or alternating two cycles each of chemotherapy and nivolumab (experimental group), with progression-free survival (PFS) as the primary endpoint. Tumour biopsies were sequenced with the TruSight Oncology 500 assay.

O que encontraram

The median tumour mutational burden (TMB; in mutations/megabase) was 8 (range, 1-13). The experimental-arm patients with TMB ≥9 or BRAF-V600E mutation (n = 17) achieved median PFS of 19.8 months (95% confidence interval, 11.3-28.3), longer (p = 0.0090) than experimental-arm patients with TMB < 9 not BRAF-V600E (n = 19) and control-arm patients with either TMB and BRAF status combination (n = 31). With TMB ≥9 or BRAF-V600E and normal, non-inflammatory level of C-reactive protein when starting nivolumab (n = 11), median PFS was 35.0 months (95% confidence interval, 6.8-63.0; p < 0.0001).

Por que isso importa

TMB, somatic BRAF status and systemic inflammation should be prospectively investigated as practical biomarkers for predicting potential responsiveness to immune checkpoint inhibitors in metastatic microsatellite-stable/mismatch repair-proficient colorectal cancer.

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.