Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

Abstract

Background Options for patients with non-squamous non-small cell lung cancer (NSCLC) whose disease progresses after first-line chemotherapy are limited. This randomized, open-label, international phase 3 study evaluated efficacy and safety of nivolumab versus docetaxel in this patient population after failure of platinum doublet chemotherapy. Methods Patients were randomized to nivolumab 3 mg per kilogram every 2 weeks or docetaxel 75 mg per square meter every 3 weeks. The primary endpoint was overall survival. Results Nivolumab improved overall survival versus docetaxel. Median overall survival was 12.2 months (95% CI, 9.7 to 15.0) for nivolumab (n=292) and 9.4 months (95% CI, 8.1 to 10.7) for docetaxel (n=290) (hazard ratio, 0.73; 96% CI, 0.59 to 0.89; P=0.002). One-year overall survival rates were 51% (95% CI, 45 to 56) for nivolumab and 39% (95% CI, 33 to 45) for docetaxel. Updated efficacy results with additional follow up are available for overall survival only: 18-month overall survival rates were 39% (95% CI, 34 to 45) for nivolumab and 23% (95% CI, 19 to 28) for docetaxel. Response rates were 19% for nivolumab and 12% for docetaxel (P=0.02). Although progression-free survival did not favor nivolumab (2.3 months for nivolumab versus 4.2 months for docetaxel), 1-year progression-free survival was higher for nivolumab (19%) than docetaxel (8%). Nivolumab further improved efficacy across all endpoints at predefined ≥1%, ≥5%, and ≥10% programmed death-1 ligand 1 (PD-L1) tumor membrane expression levels. Grade 3–5 treatment-related adverse events were reported in 10% of nivolumab and 54% of docetaxel-treated patients. Conclusions Compared to docetaxel, nivolumab demonstrated superior overall survival, with PD-L1 expression conferring enhanced efficacy in patients with advanced non-squamous NSCLC after failure of platinum-based chemotherapy. The safety profile of nivolumab was favorable versus docetaxel.

Profiles of brain metastases: Prioritization of therapeutic targets

“…The interaction between the immune system, tumor and the tumor microenvironment has been the focus of intense investigation—specifically the role of the PD‐1/PDL‐1 signaling axis,38 The efficacy of PD‐1 inhibition (i.e., nivolumab and pembrolizumab) as a monotherapy or in combination therapy has shown favorable survival in clinical trials for patients with advanced melanoma and NSCLC 39, 40, 41, 42, 43. However, the role of immune checkpoint inhibitors in the treatment of CNS cancers, including metastasis, is currently being defined,44, 45 and our current results provide further support for these agents in this context.…”

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

“…Immunotherapy using antibodies targeting checkpoint proteins has become of increasing interest and a number of clinical trials using these antibodies for several different cancer types have shown clinical responses 22, 23, 24, 25, 26, 27, 28. However, studies with animal models and cancer patients have also shown that combining antibody blockade of the PD‐1/PD‐L1 axis with other forms of immunotherapy can lead to more meaningful clinical responses 32, 33, 34, 35.…”

“…Using a different PD‐1 blockade antibody, nivolumab, clinical efficacy was shown for patients with metastatic renal cell carcinoma and for patients with ovarian cancer 26, 27. Nivolumab also increased survival of patients with non‐squamous non‐small‐cell lung cancer that resisted prior chemotherapy 28. A meta‐analysis of clinical trials involving nivolumab‐based therapy for advanced melanoma showed that treatment prolonged patient progression‐free survival 29.…”

The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions

“…Lack of activity of PD-1/PD-L1-directed agents has also been observed in patients who are never smokers and in patients with EGFR mutation-positive NSCLC [51, 52, 61]. It has been shown that NSCLC patients with tumors that have a high mutational burden have a greater probability of benefit from checkpoint inhibition [62].…”