Article : Nivolumab vs. Chemotherapy for Advanced Chemo-Naive NSCLC

Anne S. Tsao, MD reviewing Carbone DP et al. N Engl J Med 2017 Jun 22.

First-line nivolumab did not prolong progression-free survival in chemo-naive patients with stage IV or recurrent PD-L1–positive non–small-cell lung cancer.

In prior studies of first-line treatment for patients with advanced non–small-cell lung cancer (NSCLC), survival was prolonged with PD-1 inhibitor pembrolizumab versus platinum-based chemotherapy (NEJM JW Oncol Hematol Jan 2017).

To determine whether the PD-1 inhibitor nivolumab also improves survival in this setting, investigators have conducted an industry-funded, international, randomized, open-label, phase III trial (CheckMate 026), in which 423 patients with untreated stage IV or recurrent NSCLC and ≥1% PD-L1 immunohistochemical (IHC) expression received nivolumab or platinum-based chemotherapy. Chemotherapy recipients were allowed to cross over to nivolumab upon disease progression.

In patients with ≥5% PD-L1 expression, median progression-free survival (PFS, the primary endpoint) was similar with nivolumab or chemotherapy (4.2 and 5.9 months, respectively), as were overall survival (14.4 and 13.2 months) and response rate (26% and 33%). However, nivolumab was associated with a longer duration of response (12.1 vs. 5.7 months). Among patients with PD-L1 IHC ≥50%, the hazard ratio for death was 0.9 with nivolumab. Patients with high tumor-mutation burden (TMB) had higher response rates (47% vs. 28%) and longer median PFS (9.7 vs. 5.8 months). Patients with both high PD-L1 IHC and TMB had the highest response rate with nivolumab (75%). Compared with chemotherapy, nivolumab was associated with lower rates of total treatment-related adverse events (TRAEs; 71% vs. 92%) and grade 3–4 TRAEs (18% vs. 51%).


Carbone DP et al. First-line nivolumab in stage IV or recurrent non–small-cell lung cancer. N Engl J Med 2017 Jun 22; 376:2415.