Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial
By N. Rizvi, J. Mazières, D. Planchard, T. Stinchcombe, G. Dy, S. Antonia, L. Horn, H. Léna, E. Minenza, B. Mennecier and 20 more. The Lancet Oncology, 2015
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Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding Bristol-Myers Squibb.
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Citations in the corpus
- Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. (2016, background): “These findings are consistent with an emerging body of evidence supporting the hypothesis that PD-L1 expression on either TC or IC may be associated with improved response to PD-1/PD-L1 antibodies in UBC, in particular.(19,20,28,29,31) Moreover, these findings suggest that PD-L1 expression on either”
- Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. (2016, background): “A phase II trial of single-agent nivolumab was published after the systematic review; the study involved patients with SCC who had received two prior regimens.(98) Nivolumab is an anti–programmed death receptor-1 (anti–PD-1) immune checkpoint inhibitor.”
- Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. (2015, background): “Rizvi (2015) [25] II NSCLC (squamous) 117 3 mg/kg every 2 weeks Total = 74% (n = 87)”
- PD‐L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD‐L1 IHC Assay Comparison Project (2017, methodology): “Immunotherapies with checkpoint inhibitor PD-L1/PD-1 antibodies have shown encouraging results in patients with advanced Non-Small Cell Lung Cancer (NSCLC) [1-10].”
- Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. (2015, neutral): “There was an ORR of 15% in patients who had progressed after receiving at least two systemic regimens (NCT01721759) (45).”
- Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis (2017, background): “5%]) (Figure4).(18,19,21,23,31,32,36,42-46)Comparedwithpatientswhoreceived ipilimumab,patientswho receivedPD-1 inhibitorswere significantly less likely to experience any grade hypophysitis (OR, 0.”
- Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints (2016, background): “Conversely, immunotherapy approaches, specifically PD-1:PD-L1 blockade, appear to be broadly efficacious in NSCLC patients 12–14 .”