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Comment
. 2017 Jun 22;376(25):2415-2426.
doi: 10.1056/NEJMoa1613493.

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer

David P Carbone  1 , Martin Reck  1 , Luis Paz-Ares  1 , Benjamin Creelan  1 , Leora Horn  1 , Martin Steins  1 , Enriqueta Felip  1 , Michel M van den Heuvel  1 , Tudor-Eliade Ciuleanu  1 , Firas Badin  1 , Neal Ready  1 , T Jeroen N Hiltermann  1 , Suresh Nair  1 , Rosalyn Juergens  1 , Solange Peters  1 , Elisa Minenza  1 , John M Wrangle  1 , Delvys Rodriguez-Abreu  1 , Hossein Borghaei  1 , George R Blumenschein Jr  1 , Liza C Villaruz  1 , Libor Havel  1 , Jana Krejci  1 , Jesus Corral Jaime  1 , Han Chang  1 , William J Geese  1 , Prabhu Bhagavatheeswaran  1 , Allen C Chen  1 , Mark A Socinski  1 ; CheckMate 026 Investigators
Collaborators, Affiliations
Comment

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer

David P Carbone et al. N Engl J Med. .

Abstract

Background: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC.

Methods: We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more.

Results: Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy.

Conclusions: Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .).

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Figures

Figure 1.
Figure 1.. Progression-free Survival and Overall Survival among Patients with a Programmed Death Ligand 1 Expression Level of 5% or More.
CI denotes confidence interval.
Figure 2 (facing page).
Figure 2 (facing page).. Exploratory Subgroup Analyses of Progression-free Survival and Overall Survival.
Panel A shows the subgroup analysis of progression-free survival involving all the patients who underwent random ization, and Panel B the subgroup analysis of overall survival. PD-L1 denotes programmed death ligand 1. The Eastern Cooperative Oncology Group (ECOG) per formance-status score is assessed on a 5-point scale, with higher numbers indicating greater disability. Panel C shows the analysis of progression-free survival among patients who could be evaluated for tumor-mutation burden and who had a high burden. NR denotes not reached. Panel D shows the analysis of progression-free survival among patients who could be evaluated for tumor-mutation burden and who had a low or medium burden. The data for patients with a low or medium tumor-mutation burden were pooled.
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