Immunohistochemistry testing is recommended to determine the suitability for first-line CIT based on the level of PD-L1 expression, the patient’s health status, and clinical circumstances ( 3, 4). Targeted therapies, such as the anti-vascular endothelial growth factor monoclonal antibody bevacizumab, are recommended in certain combination regimens regardless of programmed death-ligand 1 (PD-L1) status ( 3). The advent of cancer immunotherapy (CIT) and targeted treatments has introduced effective first-line treatment options for metastatic and advanced disease ( 3, 4). Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancers and is the leading cause of cancer-related death ( 1, 2). These findings may support treatment decisions for patients with high PD-L1 status receiving first-line treatment for NSCLC. Survival and safety versus chemotherapy were generally similar across cancer immunotherapies and histology networks.
#Keynote 189 plus#
ORR was significantly higher with pembrolizumab and cemiplimab versus chemotherapy in the mixed-histology network, with sintilimab in the non-squamous network, and with combination regimens, including pembrolizumab or atezolizumab, in the squamous and non-squamous networks, except with atezolizumab plus carboplatin, paclitaxel, and bevacizumab. All regimens showed significantly longer expected PFS versus chemotherapy in the non-squamous network, whereas the increases were not significant in the mixed or squamous networks. OS improvements were not significant compared with chemotherapy for any regimen in the squamous and non-squamous networks, except pembrolizumab plus chemotherapy in the non-squamous network. In the mixed-histology network of PD-L1–high patients, expected OS was significantly longer with atezolizumab (estimated difference: 10.4 months ), pembrolizumab (7.2 ), and cemiplimab (13.0 ) versus chemotherapy but not with nivolumab (3.5 ) or nivolumab plus ipilimumab (6.7 ) versus chemotherapy. Heterogeneity and risk of bias were generally low across trials.
Seventeen clinical trials were included after screening 32,527 records. Hazard ratios over time with 95% credible intervals (CrIs) and expected differences in OS and PFS between each cancer immunotherapy regimen and the chemotherapy common comparator were generated. OS and PFS results were analyzed applying Bayesian fractional polynomial random-effects models. Three evidence networks were constructed based on histology (mixed, squamous, non-squamous). English records from MEDLINE and Embase published through October 2020 were eligible, supplemented by hand searches of other sources. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events. Patients with other-stage NSCLC or without PD-L1 expression and populations with < 80% stage IV NSCLC were excluded. We conducted a systematic literature review and network meta-analysis of randomized controlled trials in patients with stage IV NSCLC and high programmed death-ligand 1 (PD-L1) expression. In the absence of head-to-head trials of first-line treatments for metastatic non-small cell lung cancer (NSCLC), synthesis of available evidence is needed. 7Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.6Sandra and Edward Meyer Cancer Center, Weill-Cornell Medicine, New York, NY, United States.5York Health Economics Consortium Ltd, University of York, York, United Kingdom.4Quantics Biostatistics, Edinburgh, United Kingdom.3Access Centre of Excellence, Global Access, F.of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland 1Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, United States.
Roy Herbst 1*, Jacek Jassem 2, Seye Abogunrin 3, Daniel James 4, Rachael McCool 5, Rossella Belleli 3, Giuseppe Giaccone 6 and Filippo De Marinis 7