Promising Activity Seen With First-Line Nivolumab Plus Ipilimumab in Advanced Non–Small Cell Lung Cancer


Key Points

  • Nivolumab plus ipilimumab was active in the first-line treatment of advanced NSCLC.
  • Response rates appeared to be higher in patients with PD-L1 expression ≥ 1%.

As reported in The Lancet Oncology by Hellman et al, the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) showed promising activity as first-line treatment in patients in the non–small cell lung cancer (NSCLC) cohort of the phase I CheckMate 012 study.

Study Details

In the open-label study, patients with recurrent stage IIIb or IV disease were randomized to receive nivolumab at 1 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks; nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 12 weeks (12-week group); or nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks (6-week group). Only the latter two regimens were considered suitable for further development, with 38 patients receiving the every-12-week ipilimumab regimen and 39 receiving the every-6-week regimen.


Grade 3 or 4 treatment-related adverse events occurred in 37% of patients in the 12-week group and 33% of those in the 6-week group; the most common adverse events were increased lipase (8% and 0%), pneumonitis (5% and 3%), adrenal insufficiency (3% and 5%), and colitis (3% and 5%). Treatment-related serious adverse events occurred in 32% and 28%, and treatment-related adverse events resulted in treatment discontinuation in 11% and 13%.

Response Rates

Objective response was observed in 47% of the 12-week group and 38% of the 6-week group. After a median follow-up of 12.8 months and 11.8 months, the median duration of response had not been reached in either group. Objective response was observed in 12 of 21 patients (57%) in the 12-week group and 13 of 23 patients (57%) in 6-week group with programmed cell death ligand 1 (PD-L1) expression ≥ 1%.

The investigators concluded: “In NSCLC, first-line nivolumab plus ipilimumab had a tolerable safety profile and showed encouraging clinical activity characterised by a high response rate and durable response. To our knowledge, the results of this study are the first suggestion of improved benefit compared with anti-PD-1 [programmed cell death protein 1] monotherapy in patients with NSCLC, supporting further assessment of this combination in a phase 3 study.”

The study was funded by Bristol-Myers Squibb.

Matthew Hellmann, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.