Weight variations during first-line systemic treatment of metastatic Non-Small Cell Lung Cancer: new paradigms from Real-World Data

Purpose In studies, weight loss is strongly associated with outcomes in metastatic non-squamous cell lung cancer (mNSCLC). This work examines weight variations in first-line treatment, exploring their mechanisms based on treatment type, age, sex, weight loss and excess weight before treatment. Methods A retrospective analysis was conducted on patients undergoing first-line treatment. Weight was recorded at four points: before treatment (Wbe), day one of treatment (Wd1), three months into immune checkpoint inhibitors (ICIs) treatment or maintenance (W3mo), and at progression diagnosis (Wpro). Results Among patients (n=198), 47% received chemotherapy (CT) with ICIs, 26% CT alone, and 27% ICIs alone. At Wd1, 32% were overweight/obese (Body mass index kg/m2) (BMI ≥25). Weight loss ≥ 5% before treatment was observed in 37%. Mean (SD) weight variations between Wd1 and W3mo were -1.1% (4.6) (CT), -0.2% (7.1) (CT+ICIs), and +0.4% (7.7) (ICIs alone) (P = 0.52). Patients older than 70 compared to ≤70 lost more weight between Wd1 and Wpro (-4.7% vs. -0.4%) (P = 0.019). Patients with pre-treatment weight loss ≥ 5% compared to those without weight loss stabilized or gained weight during treatment (+2.1% vs. -1.5%) (P = 0.009). Patients with BMI ≥25 lost more weight during treatment than those with BMI <25 (-1.4% vs. +0.8%) (P = 0.024). Conclusion Weight variations did not differ significantly across treatment types. Older patients are nutritionally more vulnerable. Pre-treatment significant weight loss ≥ 5% patients stabilized or gained weight during treatment, unlike those without initial weight loss. Pre-treatment weight loss in first-line mNSCLC supports, rather than contraindicates, cancer therapy. Higher BMI was associated with greater weight loss during treatment.