Patient-focused outcomes in RELAY, a phase III trial of ramucirumab plus erlotinib (RamErl) versus placebo plus ERL (PboErl) in untreated EGFR-mutated metastatic NSCLC (EGFR+ mNSCLC)

Abstract

Background: RELAY showed significantly improved progression free survival (PFS) for RamErl over PboErlin patients with EGFR+ mNSCLC, (mPFS 19.4 vs12.4 mo; HR 0.59, 95%CI 0.46-0.76; p < 0.0001, with consistent clinical benefit in prespecified subgroups, secondary, and exploratory analyses. Safety was consistent with established profiles for Ram and Erl in NSCLC. Here, we present patient-focused outcomes. Methods: Eligible patients were randomized (1:1) to receive 150mg daily oral Erl plus 10 mg/kg intravenous Ram or Pbo Q2W until progressive disease or unacceptable tox-icity. Patients completed the Lung Cancer Symptom Scale (LCSS) and the EQ-5D at baseline, every other cycle, and the 30-day follow-up visit. Two pre-specified analyses, time to deterioration (TtD) for LCSS (secondary endpoint) and TtD in Eastern Cooperative Oncology Group performance status (ECOG PS) (exploratory endpoint) were analyzed using the Kaplan Meier method and Cox models. Changes from baseline were analyzed using a mixed-model repeated measures regression analysis. Results: Patients (93.7%) maintained ECOG PS 0/1 in both arms until progression; thus, a TtD analysis was not feasible. Overall patient compliance for LCSS and EQ-5D was high (>95%). TtD for LCSS total score (HR = 0.96 [95% CI: 0.69-1.34] and average symptomburden index TtD (HR=1.01 [95% CI: 0.73-1.40]) did not differ between treatment arms. TtD of individual LCSS items (appetite loss, fatigue, cough, shortness of breath, blood in sputum [hemoptysis], and pain; symptom distress, difficulties with daily activities, and quality of life) indicated no difference between arms, except in patient-reported hemoptysis (HR = 1.99 [95% CI: 1.21, 3.28]), which favored the PboErl arm. LCSS mean changes from baseline were consistent with TtD. Mean changes from baseline in EQ-5D index score (p = 0.94) and VAS (p = 0.95) revealed no overall differences in health status between treatment arms. Conclusions: The addition of Ram to Erl does not impair patient-focused outcomes in RELAY. These quality of life data support the clinical benefit of RamErl in untreated EGFR+mNSCLC.