Kiyotaka Yoh1, Shinji Atagi2, Martin Reck3, Edward B Garon4, Santiago Ponce Aix5, Denis Moro-Sibilot6, Katherine B Winfree7, Bente Frimodt-Moller8, Annamaria Zimmermann7, Carla Visseren-Grul9, Kazuhiko Nakagawa10. 1. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 2. Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan. 3. Lungen Clinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany. 4. David Geffen School of Medicine, University of California Los Angeles/TRIO-US Network, Los Angeles, CA, USA. 5. Hospital Universitario, CNIO Lung Cancer Clinical Research Unit, Universidad Complutense and Ciberonc, Madrid, Spain. 6. Grenoble University Hospital, Grenoble, France. 7. Eli Lilly and Company, Indianapolis, IN, USA. 8. Eli Lilly and Company, Copenhagen, Denmark. 9. Lilly Oncology, Utrecht, Netherlands. 10. Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan.
Abstract
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.
RCT Entities:
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.
Authors: Kazuhiko Nakagawa; Edward B Garon; Ling Gao; Sophie Callies; Annamaria Zimmermann; Richard Walgren; Carla Visseren-Grul; Martin Reck Journal: Cancer Chemother Pharmacol Date: 2022-07-16 Impact factor: 3.288