Nivolumab May Increase Overall Survival and Progression-Free Survival Compared to Docetaxel in Patients with Advanced Squamous Cell Non-Small Cell Lung Cancer

EBM Focus - Volume 10, Issue 24

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Reference: N Engl J Med 2015 May 31 early online (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 (Curr Opin Pharmacol 2015 Jun 1;23:32). 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 (N Engl J Med 2015 Jan 22;372(4):320, N Engl J Med 2015 Jan 22;372(4):311). Although docetaxel is currently recommended for patients with squamous cell non-small cell lung cancer with progression after first-line therapy (Chest. 2013 May;143(5 Suppl):e341S-68S, NCCN 2014 Jun), 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 non-small cell lung cancer and ≥ 2 previous treatments, with an additional 26% of patients experiencing stable disease during this phase 2 study (Lancet Oncol 2015 Mar;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 non-small 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).

Nivolumab was associated with increased overall survival with a median survival of 9.2 months compared to 6 months with docetaxel (p < 0.001). The overall survival rate at 1 year was 42% in patients treated with nivolumab and 24% in patients treated with docetaxel (p < 0.001, NNT 6). Nivolumab was also associated with increased median progression-free survival (3.5 months vs. 2.8 month, p < 0.001) and an increased rate of patients experiencing a confirmed objective tumor response (20% vs. 9%, p = 0.008, NNT 9). Any adverse event was reported in 58% with nivolumab vs. 86% with docetaxel (no p value reported), and grade 3 or 4 adverse events were reported in 7% with nivolumab vs. 55% with docetaxel (no p value reported). 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 non-small 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 non-small cell lung cancer with progression on or after platinum-based chemotherapy.

For more information see the Management of metastatic non-small cell lung cancer topic in DynaMed.