What is the role of Nibolumab (nivolumab) in treating a patient with recurrent and metastatic head and neck cancer, particularly after failing radical radiotherapy for a T1N0M0 glottic cancer?

Nivolumab for Recurrent and Metastatic Head and Neck Cancer

Nivolumab should be offered as a single agent for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed within 6 months of platinum-based chemotherapy, regardless of PD-L1 expression status. 1, 2

Evidence for Second-Line Treatment

The role of nivolumab in this clinical scenario is firmly established by high-quality evidence:

• Nivolumab demonstrated superior overall survival compared to standard chemotherapy (methotrexate, docetaxel, or cetuximab) in the CheckMate 141 trial, with median OS of 7.5 months versus 5.1 months (HR 0.70, P=0.01). 1, 3

• The 1-year survival rate was approximately 19 percentage points higher with nivolumab (36.0%) compared to standard therapy (16.6%). 1, 3

• Treatment-related grade 3-4 adverse events were significantly lower with nivolumab (13.1%) compared to standard chemotherapy (35.1%), making it a safer option with better quality of life preservation. 1, 2, 3

Key Clinical Considerations

PD-L1 testing is not required for treatment decisions, as the OS benefit with nivolumab was independent of PD-L1 expression status. 1

HPV status does not affect treatment selection, as survival benefit was observed regardless of HPV or EBV status. 1

Prior cetuximab exposure does not preclude nivolumab use. While the reduction in death risk appeared greater in cetuximab-naive patients (HR 0.52) versus those with prior cetuximab exposure (HR 0.84), nivolumab still showed efficacy in both groups. 4

Dosing and Administration

• Standard dosing: nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity. 1
• Alternative dosing of 3 mg/kg every 2 weeks was used in the pivotal CheckMate 141 trial. 3

Important Caveats

Combination therapy with radiation is not recommended outside clinical trials. The McBride trial showed no significant difference in ORR (34.5% vs 29%, P=0.86), median PFS (1.9 vs 2.6 months, P=0.79), or median OS (14.2 vs 13.6 months) when SBRT was added to nivolumab in oligometastatic HNSCC. 1

Combination with cetuximab or other agents should not be used outside clinical trials, as no combination has become standard of care in the platinum-refractory setting. 1

Prognostic Factors to Monitor

While not required for treatment initiation, baseline factors associated with better outcomes include:

• Performance status 0-1 (versus 2-3). 5
• Low neutrophil-to-lymphocyte ratio and Glasgow Prognostic Score of 0-1 correlate with improved OS. 5
• Development of immune-related adverse events during treatment is associated with better OS. 5

For Your Specific Patient

For a patient with T1N0M0 glottic cancer who failed radical radiotherapy and now has recurrent/metastatic disease:

1. Confirm platinum-based chemotherapy has been attempted (or patient progressed during/after such therapy).
2. Initiate nivolumab 240 mg IV every 2 weeks without delay for PD-L1 testing. 1, 2
3. Monitor for immune-related adverse events (pneumonitis, colitis, hepatitis, endocrinopathies) which occur less frequently than chemotherapy toxicities but require prompt recognition. 1
4. Maintain performance status as this correlates with better outcomes. 5