PS02.14 Association of Baseline Symptom Burden with Progression-Free Survival: Exploratory Analysis from the Randomized Phase III REVEL Study in NSCLC: Topic: Medical Oncology

Abstract

REVEL, a phase III randomized study (NCT01168973), demonstrated improved efficacy of ramucirumab + docetaxel versus placebo + docetaxel as second-line treatment in patients with stage IV non-small cell lung cancer (NSCLC) with progression after platinum-based chemotherapy. This exploratory analysis examined the association between baseline symptom burdens as measured by the Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index (ASBI) or total score (TS) and progression-free survival (PFS). The mean of the six symptom items - loss of appetite, fatigue, cough, dyspnea, pain, and hemoptysis - (i.e. ASBI) at baseline was calculated using the patient-reported LCSS. Low and high symptom burden (LSB < median, HSB ≥ median) were analyzed across and by treatment arms for effects on PFS using adjusted Cox proportional hazards regression models and Kaplan-Meier methods. The same analyses were conducted using TS from the LCSS, which incorporates ASBI plus symptom distress, activity level, and overall quality of life. Improved PFS was seen for patients with low symptom burden as measured by ASBI across treatment arms: LSB patients (n=265) demonstrated improved PFS over HSB (n=228) for ramucirumab + docetaxel (HR 0.716; 95% CI 0.586, 0.875) and placebo + docetaxel (LSB n=232, HSB n=269; HR 0.873; 95% CI 0.715, 1.067). When evaluating HSB patients alone, ramucirumab + docetaxel demonstrated 4.01 months (95% CI: 3.02, 4.37) vs 2.63 months (95% CI: 1.97, 2.83) median PFS while for LSB patients ramucirumab + docetaxel showed 5.39 months (95% CI: 4.27, 5.65) vs 4.27 months (95% CI: 3.75, 4.96) median PFS for placebo + docetaxel. Results for TS were similar to those for ASBI. Patients with LSB at baseline generally progress slower than patients with HSB at baseline, suggesting that symptom burden may be a prognostic factor. The preservation of improved PFS by treatment arm in the HSB cohort suggests that ramucirumab + docetaxel maintains an incremental efficacy over docetaxel alone even in those patients with poor prognosis attributed to greater symptom burden at baseline.