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
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

The EMPOWER-Lung1 study looked at patients with metastatic NSCLC and PDL1 expression >= 50%, randomized to cemiplimab vs. chemo; no surprise, the benefit was significant in the CPI therapy group. Interestingly, they allow the patients on the CPI arm to have chemo added at the time of progression, which would be a different approach. We should see more results on this as follow-up matures.


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, 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 Affiliations

1Cerrahpaşa 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

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer

FCS medical oncologist and hematologist Ernesto Bustinza-Linares, MD has co-authored an abstract published in the American Society of Clinical Oncology Journal, JCO Precision Oncology, that uncovers a new testing method to determine personalized care options for patients with metastatic non-small cell lung cancer (NSCLC). The abstract’s authors address the limitations of existing guidelines that recommend checkpoint immunotherapy, sometimes in combination with chemotherapy, for treating NSCLC, which often discounts patient variability and immune factors. The findings from the study show that by incorporating additional plasma proteome-based testing, combined with the standard protein inhibitor testing, clear differences in patient outcomes were observed after applying targeted treatments based on the testing results.

Read More »

Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor–Mutated Metastatic Non–Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722

This is the same issue as the Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04) article, this one was negative though. A question for the previous trial would be: do we need PDL-1 inhibitor, or just VEGF inhibitor, recall the pts with tumors with high PDL-1 expression did better though, so most likely we need both with chemotherapy.

Read More »

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)

Adding VEGF inhibitor to PD-1 blocker in addition to chemotherapy is better than a chemotherapy-alone regimen as a second-line therapy after TKI failure. This is true especially in patients with tumors with high PD-L1 expression, with not much besides chemotherapy as second-line therapy for those patients (or other clinical trials) that may be a better option that includes immunotherapy.

Read More »