par Lei, Ming;Overman, Michael James;Yao, Jin;André, Thierry;Lonardi, Sara;Lenz, Heinz-Josef;Aglietta, Massimo;Gelsomino, Fabio;McDermott, Ray;Wong, Ka Yeung Mark;Morse, Michael M.A.;Van Cutsem, Eric;Hendlisz, Alain 
;Cardin, Dana Backlund D.;Neyns, Bart;Hill, Andrew;Krishnamurthy, Anuradha;Chen, Franklin;Kochuparambil, Samith;Jenq, Robert R.R.;Abdullaev, Sandzhar;He, Beilei;Novosiadly, Ruslan;Kopetz, Scott
Référence Nature communications, 16, 1, 8868
Publication Publié, 2025-12
;Cardin, Dana Backlund D.;Neyns, Bart;Hill, Andrew;Krishnamurthy, Anuradha;Chen, Franklin;Kochuparambil, Samith;Jenq, Robert R.R.;Abdullaev, Sandzhar;He, Beilei;Novosiadly, Ruslan;Kopetz, ScottRéférence Nature communications, 16, 1, 8868
Publication Publié, 2025-12
Article révisé par les pairs
| Résumé : | Nivolumab alone and in combination with ipilimumab demonstrated durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer in the phase 2 CheckMate 142 study. Here, we report exploratory biomarker analyses from CheckMate 142 evaluating associations between various tissue biomarkers and the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab combination in these patients. Higher expression of inflammation-related gene expression signatures is associated with improved response per investigator assessment and survival benefit with nivolumab monotherapy. In contrast, higher tumor mutational burden, tumor indel burden, and degrees of microsatellite instability are associated with improved response per investigator assessment and survival benefit with nivolumab plus ipilimumab. While interpretation is limited by the exploratory nature of these analyses, they suggest that tumor antigenicity rather than baseline tumor inflammation might be important for the combinatorial efficacy. Validation of these findings in larger, randomized studies is necessary. |
