Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck

Abstract

BACKGROUND Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. METHODS In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. RESULTS The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P = 0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P = 0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group. CONCLUSIONS Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636.)

T cell receptor richness in peripheral blood increases after cetuximab therapy and correlates with therapeutic response

“…Immune checkpoint receptors such as PD-1 and CTLA-4, whose blockade through mAbs recently showed significant response rates in otherwise pretreated patients, 11,30 are upregulated on activated T cells. In the tumor microenvironment, T cells expressing PD-1 have been identified as clonal expansion of tumor reactive T cell populations, thus representing functionally important components in order to eliminate tumor cells.…”

“…7 Immunotherapeutic approaches targeting these pathways have demonstrated good clinical responses in a variety of tumor types. 8–11 Still, in the case of TA-specific immunity, the role of different treatment modalities on TCR properties and their therapeutic consequences is poorly understood.…”

Immunological and classical subtypes of oral premalignant lesions

“…41 Overall, the interaction between the immune system and neoplasia reflects a fundamental principle, applicable to all organ/cell types. 42 The recent success of the use of PD-1 immune checkpoint blockade in advanced HNSCC 43–45 confirms the clinical importance of immune modulation in this context. Overall, tumors orchestrate a complex signaling network to induce immune tolerance.…”

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck

“…Although the field is evolving with the development of immunotherapies and targeted therapies, we assert that regimens such as TPC could be considered instead of the EXTREME regimens in future development of definitive trials likely to involve combinations of immunotherapy and chemotherapy in this patient population [1], [2], [3], [4], [5], [6], [7], [8]. …”

“…It is worth remarking that monoclonal antibodies targeting PD‐1 have limited activity in this disease, with a response rate of only 13% in the recently published randomized controlled trial for nivolumab [5]. We suspect that the greatest benefit to the new immunotherapy compounds, either alone or in combination with other immunotherapy compounds, is likely to be realized with treatment plans that integrate immunotherapy and conventional systemic therapy.…”