NCCN Guidelines for Head and Neck Cancers V.1.2019 – Follow-Up on 01/17/2019 Guideline Page Panel Discussion/References Institution Vote and Request YES NO ABSTAIN ABSENT SALI-4/CHEM-A Based on a review of data and discussion, the panel 21 0 2 4 External request: consensus supported the inclusion of NTRK therapy (eg, larotrectinib) as an option for recurrent NTRK gene fusion- Submission from Bayer HealthCare positive salivary gland tumors with distant metastases, PS Pharmaceuticals suggesting the following for 0-3 (on page SALI-4). This is a category 2A consideration: recommendation. 1. Principles of Systemic Therapy: Add bullet “Larotrectinib is recommended for tumors harboring an NTRK gene fusion.” See Submission for references. 2. First-line Single-agent or Second- line/Subsequent Therapy: Add “larotrectinib if NTRK+” 3. Salivary Gland Tumors, Unresectable Disease or Distant Metastases: Add “larotrectinib if NTRK+” CHEM-A (1 of 6) Based on the discussion and noted references, the panel Internal request: consensus was that cetuximab + concurrent RT has limited clinical use for the primary treatment of: Panel comment to review the data for cetuximab Hypopharynx, larynx, p16-negative oropharynx 16 5 2 4 + concurrent RT as a primary definitive therapy cancers option for oropharyngeal cancer (p16-negative p16-positive oropharynx cancers 10 10 3 4 and p16-positive), hypopharyngeal cancer, and The category was changed from a category 1 to a 2B laryngeal cancer. recommendation for cancers of the oropharynx (p16- positive and p16-negative), hypopharynx or larynx. References: Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet 2019; 393(10166): 40-50. Mehanna H, Robinson M, Hartley A, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De- ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 2019; 393(10166): 51-60. NCCN Guidelines for Head and Neck Cancers V.1.2019 – Follow-Up on 01/17/2019 CHEM-A (1 of 6) Based on the discussion and noted references, the panel Internal request: consensus supported the inclusion of the following regimens for select ethmoid/maxillary sinus tumors (ie. Institutional review comment to consider small cell, SNEC, high-grade olfactory including the following regimens as options for esthesioneuroblastoma, SNUC with neuroendocrine select ethmoid/maxillary sinus tumors (ie. small features). cell, SNEC, high-grade olfactory As primary definitive therapy options: esthesioneuroblastoma, SNUC with o Cisplatin/etoposide ± concurrent RT 18 1 4 4 neuroendocrine features) o Carboplatin/etoposide ± concurrent RT 18 1 4 4 Cisplatin/etoposide ± concurrent RT o Cyclophosphamide/doxorubicin/vincristine 8 6 9 4 Carboplatin/etoposide ± concurrent RT (without concurrent RT) (category 2B) Cyclophosphamide/doxorubicin/ As first-line or subsequent-line therapy options for vincristine (without concurrent RT) recurrent, unresectable, or metastatic disease: o Cisplatin/etoposide 18 1 4 4 o Carboplatin/etoposide 18 1 4 4 o Cyclophosphamide/doxorubicin/vincristine 8 6 9 4 (category 2B) References: Patil VM, Joshi A, Noronha V, et al. Neoadjuvant chemotherapy in locally advanced and borderline resectable nonsquamous sinonasal tumors (esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation). Int J Surg Oncol 2016;2016:6923730. Resto VA, Eisele DW, Forastiere A, et al. Esthesioneuroblastoma: the Johns Hopkins experience. Head Neck 2000;22:550-558. CHEM-A (2 of 6) Based on a review of data, the panel consensus supported 14 6 3 4 External request: the inclusion of pembrolizumab as a first-line therapy option, useful in certain circumstances for patients with Submission from Merck & Co., Inc., to: recurrent or metastatic, PD-L1 positive, non- Consider the inclusion of pembrolizumab nasopharyngeal head and neck squamous cell carcinoma. monotherapy as a first-line treatment This is a category 2B recommendation. recommendation in patients with recurrent or metastatic head and neck squamous cell See Submission for references. carcinoma (HNSCC) that expresses PD-L1 combined positive score (CPS) > 1. Consider the inclusion of pembrolizumab in combination with chemotherapy with a platinum and 5-FU as a first-line treatment recommendation in patients with recurrent or metastatic HNSCC. NCCN Guidelines for Head and Neck Cancers V.1.2019 – Follow-Up on 01/17/2019 CHEM-A (2 of 6) Based on a review of data, the panel consensus was that 21 1 1 4 External request: pembrolizumab is supported by high-level evidence and the category was changed from a category 2A to a category 1 Submission from Merck & Co., Inc., requesting subsequent therapy option in patients with non- the category of evidence and consensus for nasopharyngeal, recurrent or metastatic head and neck pembrolizumab be changed from a category 2A squamous cell carcinoma with disease progression on or to a category 1 recommendation in patients with after platinum therapy. non-nasopharyngeal, recurrent or metastatic head and neck squamous cell carcinoma with See Submission for references. disease progression on or after platinum- containing chemotherapy. .