This was the first large study to show that immunotherapy works in recurrent head and neck cancer: in patients for whom platinum chemotherapy no longer worked, nivolumab raised the chance of being alive after one year from about 17% to 36%, with fewer serious side effects and better preserved quality of life.
Recurrent or metastatic disease progressing on or within 6 months after platinum-based therapy
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Nivolumab | 240 mg every 2 weeks or 480 mg every 4 weeks (in the trial: 3 mg/kg every 2 weeks) | IV, 30-minute infusion | Day 1 |
The trial excluded nasopharyngeal carcinoma, autoimmune disease and untreated brain metastases.
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Nivolumab 3 mg/kg IV over 60 minutes every 2 weeks until disease progression. Nivolumab dose reductions were not allowed (only delays or discontinuation per protocol). Current FDA-label dose for this indication: 240 mg every 2 weeks or 480 mg every 4 weeks.
Weekly IV single-agent therapy of the investigator's choice until disease progression: methotrexate 40 to 60 mg/m² weekly; or docetaxel 30 to 40 mg/m² weekly; or cetuximab 400 mg/m² loading dose, then 250 mg/m² weekly. Dose modification of these drugs according to the type and grade of adverse event was allowed.
Source of the regimen details: Full text of the paper (PMC5564292), FDA label for Opdivo (DailyMed) and ClinicalTrials.gov NCT02105636
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients aged 18 years or older with recurrent (including metastatic) squamous-cell carcinoma of the oral cavity, pharynx or larynx not amenable to curative therapy, whose disease had progressed or recurred within 6 months of the last dose of platinum-containing chemotherapy (adjuvant, with primary treatment or for recurrent disease) (platinum-refractory); ECOG 0 or 1; adequate bone marrow, hepatic and renal function; measurable disease (RECIST 1.1). Exclusion criteria: active brain metastases, autoimmune disease or systemic immunosuppression, known HIV or hepatitis B or C infection, prior immune checkpoint inhibitor therapy; according to the FDA label, nasopharyngeal carcinoma, unknown primary, salivary gland tumours and non-squamous histology were also excluded. Randomisation was stratified by prior cetuximab.
Primary endpoint: overall survival. Other endpoints: progression-free survival, objective response, safety and patient-reported quality of life.
Grade 3 or 4 treatment-related adverse events: 13.1% with nivolumab vs 35.1% with standard therapy. Among adverse events of potential immune origin: endocrine events (mainly hypothyroidism) 7.6% vs 0.9%, skin events 15.7% vs 12.6% and gastrointestinal events 6.8% vs 14.4%; pneumonitis in 2.1% of the nivolumab group. Two treatment-related deaths in the nivolumab group (pneumonitis and hypercalcaemia) and one in the standard group (lung infection). According to the FDA label, nivolumab was discontinued because of adverse events in 14% of patients and delayed in 24%. Physical, role and social functioning remained stable with nivolumab but worsened significantly with standard therapy.
CheckMate 141 led to FDA approval of nivolumab (November 2016) for recurrent or metastatic HNSCC progressing on or after platinum-based chemotherapy. Today many patients receive immunotherapy in the first line (KEYNOTE-048), but nivolumab (or pembrolizumab) remains a standard option for platinum-refractory patients without prior anti-PD-1 therapy.
Open-label design; the control group comprised three different regimens of low efficacy; progression-free survival was not improved and the response rate was low.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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