Table 1 Key clinical immunotherapy recommendations for treatment of patients with HNC

1. How should immunotherapy with PD-1 inhibitors be integrated into the treatment of recurrent/metastatic HNSCC?

First-line:

• Pembrolizumab is indicated for treatment-naïve R/M HNSCC

    ○ Pembrolizumab monotherapy may be used to treat patients with treatment naïve R/M HNSCC and PD-L1 CPS ≥1

    ○ Pembrolizumab + Chemotherapy (platinum and fluorouracil (FU)) may be used to treat all patients with treatment naïve, biomarker-unspecified R/M HNSCC patients

* Positivity for PD-L1 as ≥ 1 CPS by IHC staining

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Second-line:

• Pembrolizumab or nivolumab monotherapy should be used to treat patients with R/M HNSCC who are platinum-refractory, including those that progressed within six months of platinum-based chemotherapy

*Alternatively, if a clinical trial is available, this is the preferred option, especially if biomarker-based, hypothesis-driven

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2. What is the role of biomarker testing in patients with HNSCC?

The subcommittee recommends against standard MSI testing

Consensus

Positivity for PD-L1 is ≥1% TPS or ≥ 1 CPS by IHC staining

Consensus

The best use of biomarker testing when treating patients with HNSCC with immunotherapy is by combined positive score (CPS)

Consensus

3. How does HPV status influence the use of immunotherapy in HNSCC?

HPV status (based on p16 overexpression) should be included in treatment planning, but should not influence the decision to treat patients with R/M HNSCC with SOC immunotherapy

Consensus

4. How should treatment response be evaluated and managed in patients with advanced HNSCC?

1-month timeframe for initial clinical follow-up for identification of signs of immune-related symptoms and AEs

Consensus

For continued identification of signs of immune-related symptoms and AEs, patients to be evaluated at least monthly, and sometimes more frequently in the setting of active AEs

Consensus

In monitoring patients for signs of response after initial follow-up, patient evaluation (via radiographic imaging) should occur every three months

Consensus

If CR or near CR after treatment and six months of maintenance immunotherapy, continue treatment for at least two years or until disease progression or toxicity

Consensus

For initial assessment, conduct imaging via CT or PET-CT scan following a baseline clinical exam of the patient

Consensus

Not acceptable to treat beyond progression if a patient has symptomatic progression/clinical deterioration

Consensus

If radiographic progression is observed early in treatment, and the patient is clinically stable, continue treatment until progression is confirmed on a second scan

Consensus

If disease progression on or after treatment with a PD-1 inhibitor: enrollment in a clinical trial, treat with palliative radiotherapy and/or chemotherapy (a taxane)

Consensus

Anatomical site of the tumor is an important consideration

*potential for airway obstruction, surgical resection or radiotherapy to the site may alter the course of treatment

Consensus

The term “pseudoprogression” should be avoided in a setting of worsening symptoms

Consensus

Hyperprogression defined as “a rapid increase in tumor growth rate (minimum two-fold) compared to the expected or prior growth rate”

Consensus

5. How should immune-related adverse events be recognized and managed in patients with HNSCC?

*For further detail into toxicity management strategies please refer to the NCCN Clinical Practice Guidelines in Oncology: Management of Immunotherapy-Related Toxicities (2019)

Consensus

For an irAE < grade 3, continue ICIs for grade 1 events with the exception of some neurologic, hematologic or cardiac toxicities. For grade 2 events, stop IO therapy and provide closely monitored outpatient treatment, including consideration of oral steroids.

Consensus

For irAE development ≥ grade 3, halt treatment, admitting the patient to the hospital and administering steroids

Consensus

Routine monitoring of thyroid function, neck and airway through imaging, and AST/ALT levels

Consensus

In patients that develop hypothyroidism, continue immunotherapy, providing levothyroxine for management, and evaluating thyroid function in two-month intervals

Consensus

In the event of bulky disease leading to functional or organ compromise: halt immunotherapy

Consensus

Pneumonitis is not a greater concern in immunotherapy patients with HNSCC compared to other cancers

Consensus

6. Are there categories of patients with HNSCC who should not receive immunotherapy?

Do NOT automatically disqualify patient for anti-PD-1 immunotherapy based on: age, lung metastases, co-morbidities, auto-immune disease

Consensus

Patients with controlled diseases such as Hepatitis C or are HIV+ with normal CD4+ T cell counts and who are on antiretroviral therapy are generally suitable for ICI treatment

Consensus

7. What is the role of immunotherapy in rare head and neck cancer subtypes?

Cemiplimab should be prescribed for patients with metastatic or locally-advanced cSCC in the head and neck region who are not candidates for curative surgery or radiation

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Patients with NPC are distinct from other HNSCC patients. Clinical trial enrollment is recommended as the primary treatment option for recurrent and metastatic disease. Where clinical trial enrollment is not feasible, patients with platinum-refractory NPC may derived clinical benefit from single-agent PD-1/PD-L1 checkpoint blockade.

Consensus

8. How should immunotherapy be incorporated within a novel combination systemic therapy strategy for HNSCC?

Consensus was reached between all clinical members of the subcommittee to recommend combination therapy (notably chemotherapy + IO) for rapidly growing disease due to the need for an enhanced response rate

Consensus

9. Quality of life and Patient Engagement

Provide face-to-face counseling with patients and up-to-date literature to educate patients on how immunotherapy works and its associated toxicities

Consensus

Meet with patients plus their respective family during office visits to aid in information retention

Consensus

Treating depression in HNSCC patients with counseling and selective serotonin reuptake inhibitors (SSRIs)

Consensus

Doctors should pay close attention to depression in general appointments and should be sure to inquire into and monitor patients’ emotional well-being

Consensus

Clinical trials should be a standard part of a doctor’s discussion with the patient about their treatment options, especially for patients whose disease has recurred after first-line therapy

Consensus