COMBINATION IMMUNOTHERAPY FOR NSCLC

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.

Toxicity

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.”