Clinical and Biological Analysis in patients treated with NIVolumab plus FOLFOXIRI/Bevacizumab for Advanced COloRectal Cancer RAS or BRAF mutated: the phase II NIVACOR Trial

The phase II NIVACOR trial, an open-label, multicenter study, was designed to assess in the first-line setting, the efficacy and safety in patients affected by mCRC RAS/BRAF mutated, an anti-PD-1 antibody, nivolumab, in combination with chemotherapy triplet scheme (FOLFOXIRI) plus an anti-VEGF antibody, bevacizumab. The preliminary safety run-in analysis performed by an Independent Monitoring Committee (IDMC), after the 10th patient enrolled was conducted. The main grade 1-2 adverse events (AEs) related to FOLFOXIRI/bevacizumab affect mainly diarrhea and fatigue (71%), nausea and vomiting (57%), followed by grade 3-4 neutropenia (43%) and febrile neutropenia (14%). Grade 1-2 immune-related AEs were reported in two patients as skin rash and salivary gland infection. Two serious AEs have been reported both related to FOLFOXIRI/bevacizumab. Overall, these toxicities appear to be manageable and no major safety concerns arose. In mCRC, the coexistence of immune cell infiltration and persistent neo-angiogenesis might develop an atypical response pattern and fail the conventional criteria to detect the atypical patterns of tumor response. In the preliminary analysis in 47 patients, different exploratory criteria (RECIST 1.1., iRECIST, Choi) were performed to assess whether there was concordance. Although in a small sample of patients, these results show that there is concordance from the use of RECIST 1.1 and iRECIST criteria to evaluate the percentage variation in the sum of the diameters of the target lesions and consequently the response to treatment. More significative differences were highlighted using the Choi criteria considering the percentage variation of density in target lesions showing a higher prevalence of partial response compared to stable disease compared to RECIST Criteria.