Positive results have been reported from a phase 3, open-label, randomized study evaluating nivolumab (Opdivo, Bristol-Myers Squibb) in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SCCHN) after platinum therapy compared with the investigator’s choice of therapy (methotrexate, docetaxel, or cetuximab). Based on a planned interim analysis, the trial was stopped early in January 2016 because an assessment conducted by an independent data monitoring committee concluded that the study had met its primary endpoint of overall survival (OS) in patients receiving nivolumab compared with the control arm.
The CheckMate-141 trial evaluated nivolumab versus the investigator’s choice of therapy in patients with recurrent or metastatic SCCHN with tumor progression within six months of platinum therapy in the adjuvant, primary, recurrent, or metastatic setting. The patients were randomly assigned to receive intravenous (IV) nivolumab 3 mg/kg over 60 minutes every two weeks, or one of the following single agents: IV methotrexate 40 mg/m2 weekly; IV docetaxel 30 mg/m2 weekly; or IV cetuximab 400 mg/m2 once and then 250 mg/m2 weekly. Drugs chosen for the control arm represented the most commonly used treatments in the platinum-refractory setting. The study’s primary endpoint was OS. Secondary endpoints included the objective response rate and progression-free survival. Additional endpoints included safety.
In this study, patients treated with nivolumab experienced a 30% reduction in the risk of death, with a median OS of 7.5 months compared with 5.1 months for the investigator’s choice of therapy (hazard ratio [HR], 0.70; P = 0.0101). The one-year survival rate for nivolumab was 36% compared with 17% for the control arm.
The CheckMate-141 trial also evaluated the efficacy of nivolumab by human papillomavirus (HPV) status and programmed death ligand-1 (PD-L1) expression compared with the investigator’s choice of therapy. HPV testing was performed for patients with oropharyngeal tumors. Nivolumab demonstrated improved survival in this population, regardless of HPV status. An HPV-positive status was associated with a greater magnitude of effect with nivolumab compared with the investigator’s choice of treatment. In HPV-positive patients treated with nivolumab, median OS was 9.1 months compared with 4.4 months for patients in the control arm (HR, 0.56). In HPV-negative patients treated with nivolumab, median OS was 7.5 months compared with 5.8 months for control patients (HR, 0.73).
Cancer cells may exploit regulatory pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Nivolumab is a PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T cells and blocks the binding of PD-L1 and PD-L2, preventing the PD-1 pathway’s suppressive signaling on the immune system, including interference with an antitumor immune response.
In July 2014, nivolumab was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world.
In the U.S., nivolumab is approved for the treatment of patients with:
Source: Bristol-Myers Squibb; April 19, 2016.