e15638 Background: Dual-agent regimens such as CAPOX and FOLFOX have demonstrated significant tumor downstaging efficacy in the neoadjuvant treatment of locally advanced colorectal cancer (LACC). In contrast, the triple-agent regimen FOLFOXIRI, while potentially superior in metastatic settings, has limited clinical utility owing to its poor tolerability profile.. Liposomal irinotecan, an optimized formulation of irinotecan, reduces adverse events through enhanced drug delivery, thereby improving the feasibility of triple-drug combination therapy. This trial aimed to evaluate the efficacy and safety of the NALIRIFOX regimen as neoadjuvant therapy for LACC. Methods: Patients with advanced colon cancer (cT4N1-2M0) or upper/middle rectal cancer (cT3-4N0-2M0, MRF+/EMVI+) who were candidates for R0 resection with anal preservation were enrolled. Eligible patients received NALIRIFOX (liposomal irinotecan 50 mg/m², oxaliplatin 60 mg/m², leucovorin 400 mg/m², fluorouracil 2400 mg/m²) every two weeks for 4–8 cycles, followed by surgical resection. The primary endpoint was the pathological complete response (pCR) rate. Key secondary endpoints included downstaging rate, R0 resection rate, tumor regression grade (TRG), perioperative complications, 2-year recurrence rate, disease-free survival (DFS), and safety. Results: From December 2024 to June 2025, 30 patients were enrolled. One patient with posterior uterine wall metastasis was inadvertently included and postoperatively confirmed to have malignant disease. The median age was 58 years (range 37–75), and 27 patients (90.0%) had stage III disease. Of these, 28 patients (93.3%) completed 4–8 cycles of chemotherapy, and 27 patients (90.0%) underwent surgery, achieving a 100% R0 resection rate. One 75-year-old patient discontinued treatment due to an adverse event (AE), while two declined surgery for personal reasons. No postoperative complications were reported. The pCR rate was 7.4% (2/27), and 77.8% (21/27) of patients achieved TRG 1–2. Tumor downstaging was observed in 85.2% (T stage), 74.1% (N stage), and 63.0% (TNM stage) of patients. Treatment-emergent adverse events (TEAEs) of any grade occurred in all 30 patients, with 4 (13.3%) experiencing grade ≥3 events; all four completed at least 4 treatment cycles. The most common grade ≥3 TEAEs were intestinal obstruction (6.7%), leukopenia (3.3%), and neutropenia (6.7%). Conclusions: The triple-agent neoadjuvant regimen containing liposomal irinotecan, oxaliplatin, and 5-fluorouracil/leucovorin demonstrated promising efficacy in patients with LACC, reflected in substantial tumor downstaging. The regimen also showed a favorable and manageable safety profile, supporting further investigation as a potential neoadjuvant treatment option for LACC. Clinical trial information: ChiCTR2400092630.
Hou et al. (Thu,) studied this question.