Level 2 (mid-level) evidence


Programmed death 1 (PD-1) receptors on activated T cells interact with PD-1 ligands expressed on tumor cells, suppressing immune activation and promoting tumor immune evasion. Anti-PD-1 antibodies have been shown to improve survival compared to chemotherapeutic agents in patients with not previously treated advanced melanoma and relapsed or refractory Hodgkin lymphoma. Although docetaxel is currently recommended for patients with squamous cell non-small cell lung cancer with progression after first-line therapy, recent evidence suggests anti-PD1 antibodies may be effective in this patient population as well. The anti-PD-1 antibody nivolumab has previously been shown to produce an objective response in 14.5% of patients with advanced squamous cell lung cancer and ≥ 2 previous treatments, with an additional 26% of patients experiencing stable disease during this phase 2 study (Lancet Oncol. 2015;16[3]:257). A recent randomized trial compared nivolumab 3 mg/kg IV every 2 weeks vs. docetaxel 75 mg/m2 IV every 3 weeks in 272 patients with advanced squamous cell lung cancer experiencing disease recurrence after treatment with platinum-containing regimens. All patients had stage IIIB or stage IV disease and an Eastern Cooperative Oncology Group performance-status score of 0-1. Patients were treated until disease progression or discontinuation due to adverse events (or other reasons) (N Engl J Med. 2015; May 31 early online)


Nivolumab was associated with increased overall survival with a median survival of 9.2 months compared to 6 months with docetaxel. The overall survival rate at 1 year was 42% in patients treated with nivolumab and 24% in patients treated with docetaxel (NNT 6). Nivolumab was also associated with increased median progression-free survival (3.5 months vs. 2.8 month) and an increased rate of patients experiencing a confirmed objective tumor response (20% vs. 9%, NNT 9). Any adverse event was reported in 58% with nivolumab vs. 86% with docetaxel, and grade 3 or 4 adverse events were reported in 7% with nivolumab vs. 55% with docetaxel. PD-1 ligand expression in pretreatment tumor samples was not associated with nivolumab efficacy.


Compared to standard docetaxel therapy, nivolumab increased median overall survival by > 3 months, with nearly twice as many patients surviving 1 year after treatment initiation. The rate of progression-free survival at 1 year was also more than 3 times greater with nivolumab compared to docetaxel and significantly more patients had a complete or partial tumor response. Not only was nivolumab more effective than docetaxel, but it also had a better safety profile, with a drastic reduction in the number of serious adverse events reported in the nivolumab group. Tumor PD-1 ligand expression did not predict patient response, suggesting nivolumab effectiveness may not be limited to patients with high pre-treatment levels of PD-1 ligand. The results of this trial suggest that nivolumab may not only be more effective than docetaxel as a second-line therapy in patients with advanced squamous cell lung cancer, but it may also be safer. These results combined with previous data have led the FDA to approve nivolumab for patients with metastatic squamous cell lung cancer with progression on or after platinum-based chemotherapy. 



Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester. 

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