July 2015, Special ASCO Edition

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Nivolumab Is Superior to Docetaxel as Second-Line Therapy for Patients with NSCLC

Immunotherapy

Immunotherapy with the programmed death-1 (PD-1) inhibitor nivolumab as second-line therapy prolonged survival in patients with nonsquamous non–small cell lung cancer (NSCLC) who had experienced disease progression with standard platinum-based therapy. The patients in the nivolumab group lived an average of 3 months longer 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-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 on previous standard therapy. Patients were randomized to nivolumab every 2 weeks or to docetaxel every 3 weeks until disease progression or discontinuation resulting from toxicity or other reasons. One previous treatment was allowed, and the study accepted patients regardless of PD-L1 expression.

Median OS, the primary end point, was 12.2 months for nivolumab and 9.4 months for docetaxel, reflecting a 27% decrease in the risk of death in the patients receiving nivolumab (P = .0015). One-year OS was 51% for patients receiving nivolumab and 39% for those receiving docetaxel.

The overall response rate (ORR) was 19.2% for nivolumab and 12.4% for docetaxel (P = .0246). 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.

Median progression-free survival (PFS) was 2.3 months with nivolumab and 4.2 months with docetaxel, which was not statistically significant. One-year PFS was 19% and 8%, respectively.

The 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 for those treated 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.

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.

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 but still receive a benefit from nivolumab. Thus, the search continues for a better biomarker, Paz-Ares noted.

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