G8 screening-defined geriatric vulnerability as a predictor of survival and quality of life in older patients with advanced cancer treated with novel therapies.

1663 Background: Older patients with advanced cancer are a highly heterogeneous population, in whom geriatric vulnerability may significantly influence survival, treatment tolerance, and patient-reported outcomes. The G8 screening tool is a validated instrument designed to identify geriatric vulnerability and select patients for comprehensive geriatric assessment; however, its prognostic and longitudinal impact on quality of life in patients receiving novel anticancer therapies remains poorly explored. Methods: The ONC-OLD study prospectively enrolled patients aged ≥70 years with advanced cancer treated with novel therapies across six referral centers. The primary objective was to assess the prognostic impact of baseline G8-defined geriatric vulnerability on overall survival (OS). Geriatric vulnerability was assessed at baseline using the G8 screening tool (≤14 vs >14). Health-related quality of life (HRQoL) was assessed using the EORTC QLQ-C30 and QLQ-ELD14 at baseline, after 3 months, and at disease progression. Baseline associations were analyzed using multivariable regression models, while longitudinal HRQoL changes were assessed using ANCOVA adjusted for baseline scores and relevant clinical covariates. Results: A total of 143 patients were included (median age 78 years, IQR 75-82); 78% had ECOG performance status (PS) 0-1, and 73% had G8 ≤14. Treatments consisted mainly of immunotherapy, either as monotherapy (31%) or in combination (36%), and targeted therapy (30%). At baseline, patients with G8 ≤14 were older (≥80 years: 46% vs 20%, p=0.019), more frequently female (42% vs 16%, p=0.016), and had worse ECOG PS (PS ≥2: 25% vs 0%, p=0.005) compared with those with G8 >14, with a different distribution of primary tumor types (lung cancer: 67% vs 29%, p=0.001). Median OS was 16.1 months (95% CI, 13.4-not reached) and was significantly shorter in patients with G8 ≤14 compared with those with G8 >14 (14.2 vs not reached; p=0.019). G8 ≤14 was independently associated with an increased risk of death (HR 2.71, 95% CI 1.01-7.24; p=0.047), after adjustment for ECOG PS, number of metastatic sites, treatment line and type. G8 ≤14 was associated with a trend toward a higher risk of grade ≥3 adverse events (OR 2.00, 95% CI 0.69-7.25; p=0.23), without specific treatment-related safety signals. At baseline, patients with impaired G8 reported worse global health, physical and role functioning, fatigue, pain, and mobility (all p≤0.01). In longitudinal analyses adjusted for baseline HRQoL and clinical covariates (ECOG PS, age, treatment), G8 remained significantly associated with higher fatigue (+12.6 points; p=0.039). Conclusions: Baseline G8 impairment is associated with poorer survival, worse baseline HRQoL, and a higher risk of severe toxicity, supporting the clinical value of G8 screening in older patients treated with novel therapies.