Patient-reported outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small-cell lung cancer

Science and Research

OBJECTIVE: In the phase 3 RELAY trial, ramucirumab/erlotinib demonstrated superior progression-free survival (PFS) over placebo/erlotinib in patients with EGFR-mutated metastatic NSCLC (median PFS 19.4 versus 12.4 months; HR = 0.59, 95% CI = 0.46-0.76; p < .0001). Safety was consistent with established profiles for ramucirumab and erlotinib in NSCLC. Here, we present patient-reported outcomes. METHODS: Patients received oral erlotinib (150 mg daily) plus intravenous ramucirumab (10 mg/kg) or placebo Q2W until progressive disease or unacceptable toxicity. Patients completed the Lung Cancer Symptom Scale (LCSS) and EQ-5D questionnaires at baseline and every other cycle. Analyses included time to deterioration (TtD) for LCSS via Kaplan-Meier method and Cox models and changes from baseline using mixed-model repeated-measures regression analysis. RESULTS: Overall patient compliance for LCSS and EQ-5D was >95%. TtD did not differ between treatment arms for LCSS Total Score (HR = 0.962, 95% CI = 0.690-1.343) and Average Symptom Burden Index (HR = 1.012, 95% CI = 0.732-1.400). TtD of individual LCSS items (appetite loss, fatigue, cough, shortness of breath, pain, symptom distress, difficulties with daily activities, quality of life) indicated no difference between arms; however, patient-reported blood in sputum was worse for ramucirumab/erlotinib (HR = 1.987, 95% CI = 1.206-3.275). Results of LCSS mean changes from baseline were consistent with TtD, indicating no significant differences between treatment arms except for blood in sputum. Mean changes from baseline in EQ-5D index score (p = .94) and visual analogue scale (p = .95) revealed no overall differences in health status between treatment arms. CONCLUSIONS: Patients' overall quality of life and symptom burden did not differ with the addition of ramucirumab to erlotinib compared to placebo/erlotinib. These data support the clinical benefit of ramucirumab/erlotinib in untreated EGFR-mutated metastatic NSCLC.