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

Abstract

Background Patients with advanced squamous-cell non–small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint–inhibitor antibody, as compared with docetaxel in this patient population. Methods We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. Results The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P = 0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group. Conclusions Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.)

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.…”

Pulmonary pleomorphic carcinoma with pseudoprogression during nivolumab therapy and the usefulness of tumor markers: A case report

“…Some patients were reported to present with tumor shrinkage after significant growth during ICI therapy 4. This finding is called pseudoprogression and has been reported to occur in 5.1%‐6.7% of patients with NSCLC during nivolumab therapy 1, 2. Pseudoprogression in PPC has also been reported;6 however, it is rare and has only been described in a few case reports.…”

A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint

“…In particular, PD-L1-blocking antibodies, such as atezolizumab, avelumab, and durvalumab, showed prominent clinical activity in patients with advanced stage melanoma 8-10 and non-small-cell lung carcinoma (NSCLC). 11 , 12 However, the efficacy of current conventional monospecific PD-L1-blocking antibodies is potentially hampered due to on-target/off-tumor binding to numerous normal cell types that also express PD-L1. In this respect, binding to PD-L1-expressing cells in blood or other tissue may prevent antibody extravasation and accumulation at the site of the tumor.…”