NICOLAS is the first completed single-arm phase II trial in stage III non-small-cell lung cancer ( NSCLC ) examining hierarchically first the safety and then the efficacy of adding Nivolumab ( Opdivo ) concurrently to standard definitive concurrent chemo-radiotherapy.
The safety endpoint was reported earlier.
Researchers have presented the efficacy results.
Stage IIIA/B unresectable treatment-naive NSCLC patients received 3 cycles of Platinum-based chemotherapy and concurrent radiotherapy ( 66Gy/33 fractions ), along with Nivolumab ( 360mg/Q3W ).
Nivolumab was continued as monotherapy consolidation for a maximum of one year ( 480mg/Q4W ).
The primary endpoint was 1-year progression-free surival ( PFS ), with a target improvement compared to historical data of at least 15%, from 45% to 60%.
For testing this efficacy hypothesis, a sample size of 74 evaluable patients provides power 83%, at 1-sided alpha 5%.
79 patients were enrolled with median follow-up 21.0 months ( interquartile range:15.8-25.8 months ) for the primary PFS analysis.
35.4% of patients had stage stage IIIA and 63.3% stage IIIB.
The 1-year progression-free survival was 53.7% ( 95% CI [ 42.0-64.0% ] ), the median progression-free survival 12.7 months ( 95% CI [ 10.1-22.8 months ] ).
Since among the 74 first evaluable patients, 37 PFS events occurred in the first year post-treatment, a 1-year PFS rate of less than or equal to 45% could not be rejected ( p-value=0.23 ).
At an extended follow-up ( 32.6 months median ), 37 deaths have been recorded, with a median overall survival ( OS ) 38.8 months ( 95% CI [ 26.8 months - Not-Estimable ] ) and a 2-year OS rate of 63.7% ( 95% CI [ 51.9-73.4% ] ).
The overall survival of stage IIIA patients was found to be significantly higher than stage IIIB patients, with 2-year overall survival 81% and 56% respectively ( p=0.037 ).
In conclusion, progression-free survival and overall survival are arithmetically higher to studies in the same population, however, based on the formal hierarchical efficacy analysis, researchers could not reject that the 1-year PFS rate is less than or equal to 45%. ( Xagena )
Peters S et al, J Thorac Oncol 2020; Online ahead of print