Nivolumab Beats Docetaxel as Second-Line Therapy for Patients with NSCLC

Phoebe Starr

August 2015, Vol 6, No 7 - Emerging Therapies

Chicago, IL—Immunotherapy with the anti–PD-1 agent nivolumab (Opdivo) prolonged survival in patients with nonsquamous non–small-cell lung cancer (NSCLC) as second-line therapy for disease progression with standard platinum-based therapy, based on results of CheckMate 057, which were presented at the 2015 American Society of Clinical Oncology meeting.

Nivolumab had the best outcomes in patients whose tumors had high PD-1 ligand 1 (PD-L1) expression. Overall survival (OS) was almost 2 times higher with nivolumab than with docetaxel across all levels of PD-L1.

“Nivolumab is the first PD-1 inhibitor to significantly improve overall survival 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.

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 resulting from toxicity or another reason. One previous treatment was allowed, and the study ­accepted patients regardless of PD-L1 expression.

For the primary end point, the median OS times were 12.2 months for nivolumab and 9.4 months for docetaxel, reflecting a 27% decrease in the risk for death in the 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) times were 2.3 months with nivolumab and 4.2 months with docetaxel, which was an insignificant difference. The 1-year PFS rates were 19% and 8%, respectively, in the cohorts.

The PD-L1 expression was assessed using the cutoffs of ≥1%, ≥5%, and ≥10%, and PD-L1 expression level was predictive of survival.

At the highest level of PD-L1 expression (≥10% of cells), the median OS times were 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 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 lower with nivolumab at 69% 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 groups receiving nivolumab and docetaxel, respectively; the rates of grade 3 or 4 serious adverse events were 5% and 18%, respectively.

The 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, some patients do not express PD-L1 and still benefit from nivolumab. Thus, the search continues for a better biomarker, Dr Paz-Ares noted.