Is PDL1 (Programmed Death-Ligand 1) testing needed for a patient with oropharyngeal cancer who has progressed on gemcitabine/cisplatin and paclitaxel/cisplatin before starting immunotherapy with nivolumab (Opdivo) or pembrolizumab (Keytruda)?

PD-L1 Testing for Oropharyngeal Cancer Before Immunotherapy

PD-L1 testing is NOT required before starting nivolumab or pembrolizumab in patients with platinum-refractory recurrent/metastatic oropharyngeal cancer, though it provides prognostic information that may guide treatment selection between these agents.

Regulatory Approval and Treatment Access

• Nivolumab is FDA-approved without PD-L1 testing requirements for recurrent or metastatic head and neck squamous cell carcinoma that has progressed on or after platinum-based chemotherapy 1
• Pembrolizumab is FDA-approved without mandatory PD-L1 testing in the same setting, though PD-L1 expression data can inform treatment decisions 1
• Both agents can be initiated immediately without waiting for PD-L1 test results, as they work independently of PD-L1 expression 2

Evidence-Based Treatment Recommendations

Nivolumab (Category 1 Recommendation)

• NCCN recommends nivolumab as a Category 1 option based on high-quality randomized trial evidence showing survival benefit over standard single-agent chemotherapy 1
• Nivolumab prolongs overall survival regardless of PD-L1 status, though patients with PD-L1-positive tumors derive greater survival benefit 1
• Grade 3/4 adverse events occurred in only 13.1% of nivolumab-treated patients 1

Pembrolizumab (Category 2A Recommendation)

• NCCN recommends pembrolizumab as a Category 2A option based on non-randomized trial data 1
• In patients with PD-L1-positive tumors (≥1% expression), pembrolizumab achieved a 22% response rate versus only 4% in PD-L1-negative patients (P=0.021) 1
• Overall response rate was 18% with 6-month OS of 59% in the expansion cohort 1

Clinical Decision Algorithm

When PD-L1 testing is available:

• If PD-L1 CPS ≥1: Consider pembrolizumab for higher likelihood of response (22% vs 4%) 1, or nivolumab for Category 1 evidence and favorable toxicity profile 1
• If PD-L1 negative: Prefer nivolumab given its Category 1 recommendation and proven survival benefit independent of PD-L1 status 1

When PD-L1 testing is unavailable or delayed:

• Proceed immediately with nivolumab (preferred due to Category 1 evidence) 1
• Do not delay treatment waiting for PD-L1 results 2

Important Caveats

• PD-L1 testing definitions and scoring methods vary between trials, creating ambiguities in interpretation 1
• PD-L1 expression is prognostic but not absolutely predictive—responses occur in PD-L1-negative patients with both agents 1
• For first-line recurrent/metastatic disease with PD-L1 CPS ≥1, pembrolizumab combined with platinum/5-FU is a distinct treatment option with different approval criteria 1
• The most recent ESMO guidelines (2020) validate PD-L1 IHC testing using FDA-approved assays specifically for identifying patients who may benefit from first-line pembrolizumab monotherapy in recurrent/metastatic disease 1

Practical Implementation

• Nivolumab dosing: 240 mg IV every 2 weeks 2
• Pembrolizumab dosing: 200 mg IV every 3 weeks 1, 2
• Both agents demonstrated durable responses in HPV-associated and non-HPV-associated oropharyngeal cancers 1
• Treatment should be discussed in a multidisciplinary team setting 1, 3