Immunonutrition intervention in driver gene–negative non–small cell lung cancer patients with sarcopenia: A randomized controlled trial.

Abstract

8587 Background: Cancer-related sarcopenia impairs treatment tolerance and survival in advanced NSCLC. This Phase II trial evaluated IMPACT (arginine and omega-3 enriched formula) in driver gene-negative advanced NSCLC patients receiving chemoimmunotherapy. Methods: Single-center, open-label, randomized Phase II study. Eligible patients: driver gene-negative advanced NSCLC with sarcopenia (AWGS criteria). Randomization 1:1 to IMPACT plus chemoimmunotherapy (Arm A, n=59) versus chemoimmunotherapy alone (Arm B, n=49). IMPACT administered continuously during treatment. Primary endpoint: PFS. Secondary endpoints: body composition (BIA, CT-L3), inflammatory markers (NLR), nutritional status (PG-SGA), safety. Statistical design: 80% power, HR=0.60, alpha=0.05. Dropouts: 7 (11.9%) in Arm A, 5 (10.2%) in Arm B. Modified ITT: 96 patients (52 vs 44). Results: Baseline characteristics balanced. Median PFS: not reached (Arm A) versus 7.0 months (95% CI: 5.2-8.8, Arm B); HR=0.45 (95% CI: 0.23-0.88), P=0.018. Six-month PFS: 82.7% versus 54.5%; 12-month PFS: 59.6% versus 31.8%. NLR change: -1.28 versus +0.16 (P=0.0045). Lean mass change: +0.59 kg versus -1.00 kg (P<0.05). L3 skeletal muscle density: +1.93 HU versus +0.37 HU (P<0.05). PG-SGA improved in Arm A (9.1±5.6 to 6.4±5.1, P<0.001) but not Arm B (8.9±5.8 to 8.2±5.5, P=0.156). Elderly subgroup (≥65y) showed enhanced benefit: HR=0.23 (95% CI: 0.06-0.95), P=0.043. Grade 3-4 AEs: 38.5% versus 52.3% (P=0.156). No IMPACT-related SAEs. Conclusions: IMPACT immunonutrition with chemoimmunotherapy significantly improved PFS, preserved lean mass, reduced inflammation, and enhanced nutritional status in driver gene-negative advanced NSCLC with sarcopenia. Well-tolerated with favorable safety. Phase III evaluation warranted. Clinical trial information: ChiCTR2300078741. Key efficacy outcomes. Endpoint Arm A (Sustagen, n=52) Arm B (Control, n=44) P value edian PFS, months NR 7.0 (5.2-8.8) 0.018 6-month PFS, % 82.7 54.5 - 12-month PFS, % 59.6 31.8 - NLR change -1.28 +0.16 0.0045 Lean mass change, kg +0.59 -1.00 <0.05 L3 SMD change, HU +1.93 +0.37 <0.05