Immunotherapy with the recently approved anti–PD-1 inhibitor nivolumab prolonged survival in patients with nonsquamous non–small-cell lung cancer (NSCLC) as second-line therapy for disease progression with standard platinum-based therapy. The patients in the nivolumab group had an average of 3 months longer of survival compared with patients receiving docetaxel in the phase 3, randomized, controlled CheckMate 057 trial. Moreover, adverse events were less severe with nivolumab than with docetaxel.
Nivolumab had the best outcomes in patients whose tumors had high PD ligand 1 (PD-L1) expression. Overall survival was almost twice as high with nivolumab than with docetaxel across all levels of PD-L1.
“Nivolumab is the first PD-1 inhibitor to significantly improve overall survival (OS) versus docetaxel in previously treated patients with advanced nonsquamous NSCLC, the most common form of lung cancer,” said Luis G. Paz-Ares, MD, PhD, Professor of Medicine at Hospital Universitario Virgen Del Rocio, Seville, Spain, at ASCO 2015.
CheckMate 057 included 582 patients with stage III or IV advanced nonsquamous NSCLC that progressed with previous standard therapy. Patients were randomized to nivolumab every 2 weeks or to docetaxel every 3 weeks until progression or until discontinuation because of toxicity or another reason. One previous treatment was allowed, and the study accepted patients regardless of PD-L1 expression status.
For the primary end point, the median OS was 12.2 months for nivolumab and 9.4 months for docetaxel, a 27% decrease in mortality risk in patients receiving nivolumab (P = .001). The 1-year OS rates were 51% for patients receiving nivolumab and 39% for those receiving docetaxel.
The overall response rates (ORRs) were 19.2% for nivolumab and 12.4% for docetaxel (P = .024). The median duration of response was 17.1 months with nivolumab versus 5.6 months with docetaxel.
The ORR was 36% in patients with the highest level of PD-L1 expression.
The median progression-free survival (PFS) was 2.3 months with nivolumab and 4.2 months with docetaxel. The 1-year PFS rates were 19% and 8%, respectively, in these cohorts.
PD-L1 expression was assessed using the cutoffs of ≥1%, ≥5%, and ≥10%, and the level of PD-L1 expression was predictive of survival.
At the highest level of PD-L1 expression (≥10% of cells), the median OS was 19 months with nivolumab and 8 months with docetaxel. The median OS was substantially higher with nivolumab compared with docetaxel in patients with PD-L1 of ≥1% and ≥5%. Depending on the level of PD-L1 expression, the median OS ranged from 17.2 months to 19.4 months.
No difference in median OS was observed between the 2 treatment arms in patients with low PD-L1 expression (<10% of cells).
The rate of treatment-related adverse events was 69% with nivolumab versus 88% in the docetaxel group. The rates of grade 3 and 4 adverse events were 10% in the nivolumab group and 54% in the docetaxel group.
Serious adverse events were reported in 7% and 20% of the patients receiving nivolumab and docetaxel, respectively; the rates of grade 3 or 4 serious adverse events were 5% and 18%, respectively.
Treatment-related discontinuations occurred in 5% of the patients receiving nivolumab and in 15% of the patients receiving docetaxel.
Although PD-L1 expression was correlated with survival and response rates, there are patients who do not express PD-L1 and who benefit from nivolumab. Thus, the search continues for a better biomarker, Dr Paz-Ares noted.