First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial
Author(s): Prof Mustafa Özgüroğlu, MD1; Prof Saadettin Kilickap, MD2; Prof Ahmet Sezer, MD3; Prof Mahmut Gümüş, MD4; Prof Igor Bondarenko, MD5; Miranda Gogishvili, MD6; Marina Nechaeva, MD7; Prof Michael Schenker, MD8; Prof Irfan Cicin, MD9; Prof Gwo Fuang Ho, MD10; Yaroslav Kulyaba, MD11; Kasimova Zyuhal, MD12; Roxana-Ioana Scheusan, MD13; Prof Marina Chiara Garassino, MD14; Xuanyao He, PhD15; Manika Kaul, MD15; Emmanuel Okoye, MPH15; Yuntong Li, PhD15; Siyu Li, PhD15; Jean-Francois Pouliot, PhD15; Frank Seebach, MD15; Israel Lowy, MD15; Giuseppe Gullo, MD15; Petra Rietschel, MD15
Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months’ follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.
EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator’s choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.
Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months’ follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1–31·8; 149 [52%] of 284 died) versus 13·3 months (10·5–16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46–0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2–8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3–6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42–0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1–9·3) and overall survival of 15·1 months (11·3–18·7). The most common grade 3–4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals
At 35 months’ follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.
Regeneron Pharmaceuticals and Sanofi.
Author Affiliations1Cerrahpaşa Faculty of Medicine, Division of Medical Oncology, Istanbul University Cerrahpaşa, Istanbul, Türkiye; 2Faculty of Medicine, Department of Internal Medicine and Medical Oncology, Istinye University Istanbul, Türkiye; 3Department of Medical Oncology, Başkent University, Adana, Türkiye; 4Department of Medical Oncology, School of Medicine, Istanbul Medeniyet University, Istanbul, Türkiye; 5Department of Oncology and Medical Radiology, Dnipropetrovsk Medical Academy, Dnipro, Ukraine; 6High Technology Medical Centre, University Clinic, Tbilisi, Georgia; 7Division Arkhangelsk Clinical Oncology Center, Arkhangelsk, Russia; 8Centrul de Oncologie Sf Nectarie SRL, Craiova, Romania; 9Department of Medical Oncology, Trakya University, Edirne, Türkiye; 10Clinical Oncology Unit, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 11Prognosis Optima LLC, Kyiv, Ukraine; 12Multiprofile Hospital for Active Treatment, Dobrich, Bulgaria; 13Oncocenter Oncologie Clinica, Timisoara, Romania; 14Department of Medicine, Section of Hematology/Oncology, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA; 15Regeneron Pharmaceuticals, Tarrytown, NY, USA