First-line Nivolumab plus FOLFOXIRI/Bevacizumab in advanced RAS/BRAF-mutated colorectal cancer: efficacy, safety and...

Area of Science:

• Oncology
• Gastroenterology
• Immunotherapy

Background:

• Immunotherapy is effective for dMMR/MSI mCRC but limited in pMMR/MSS mCRC.
• Novel treatment strategies are needed for pMMR/MSS metastatic colorectal cancer.
• RAS/BRAF mutations are common in mCRC and impact treatment outcomes.

Purpose of the Study:

• To evaluate the efficacy and safety of FOLFOXIRI/bevacizumab plus nivolumab in first-line treatment of RAS/BRAF-mutated mCRC.
• To assess the Objective Response Rate (ORR) as the primary endpoint.
• To explore genomic and transcriptomic profiles associated with treatment response.

Main Methods:

• Phase II NIVACOR trial (NCT04072198) enrolled 73 patients with RAS/BRAF-mutated mCRC.
• Patients received first-line FOLFOXIRI/bevacizumab plus nivolumab.
• Objective Response Rate (ORR), progression-free survival (PFS), overall survival (OS), safety, and quality of life were assessed.
• Comprehensive genomic profiling and RNA sequencing were performed.

Main Results:

• The ORR was 76.7% (95% CI, 65.4 to 85.8%), meeting the primary endpoint.
• Disease control rate was 97.3% (95% CI, 90.5 to 99.7%).
• Median PFS was 10.1 months (95% CI, 9.0 to 14.3 months); median OS was not reached.
• Grade 3 or higher treatment-related adverse events occurred in 65.8% of patients.
• Genomic alterations in PI3K/AKT, chemokine signaling, and DNA repair pathways correlated with treatment activity.

Conclusions:

• FOLFOXIRI/bevacizumab plus nivolumab demonstrates significant activity in pMMR/MSS RAS/BRAF-mutated mCRC.
• This combination therapy represents a potential new first-line option for selected mCRC patients.
• Genomic profiling can identify biomarkers predictive of response to this combination therapy.