PURPOSE Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. PATIENTS AND METHODS Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS). RESULTS The study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m2. EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively. CONCLUSION Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.

6011 Background: Pembrolizumab (pembro) is a humanized monoclonal antibody that blocks the programmed death receptor-1 (PD-1) interaction with its ligands (PD-L1, PD-L2). While pembro is approved for platinum-refractory, recurrent/metastatic SCCHN, its role in definitive therapy for LA-SCCHN is not yet defined. Here we present the safety results of pembro with cisplatin-based CRT for patients (pts) with LA-SCCHN (NCT02586207). Methods: 27 pts with oropharyngeal (OP), hypopharyngeal (HP), and laryngeal (L) stage III-IVB SCCHN (any HPV status) eligible for cisplatin-based, definitive CRT were enrolled from November 2015 to August 2016 as part of a safety cohort. Pembro was given at a fixed dose of 200 mg IV 4-7 days prior to initiation of CRT and then every 3 weeks during CRT (2 concomitant doses) and then following CRT for 5 additional doses. CRT consisted of weekly cisplatin 40 mg/m2 IV x 6 doses (240 mg/m2 maximum) given concurrently with radiation at a dose of 2 Gy once daily for 35 fractions (total 70 Gy). Safety was determined by the occurrence of CRT or pembro dose-limiting adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on imaging or with salvage surgery at 100 days post-CRT completion. Results: 20 (74%) pts with OP HPV+ and 7 (26%) pts with HPV- (4 L, 2 OP, 1 HP) tumors were enrolled. 21 (78%) completed all planned doses of pembro. 3 discontinued due to irAEs (G2 peripheral motor neuropathy, G3 AST elevation, G1 Lhermitte-like syndrome). 3 discontinued due to protocol reasons (early neck dissection -2 pts, prolonged hospitalization-1 pt). All pts completed the full radiation dose (70 Gy) without significant delay (defined as > 5 days). 23 (85%) received the goal target dose of cisplatin (≥200 mg/m2). There was one pt death due to concurrent illness, unrelated to treatment. The study has been reopened with expansion cohorts of 34 HPV+ pts and 23 HPV- pts to evaluate efficacy. Conclusions: Pembro in combination with weekly cisplatin-based CRT is safe and does not significantly impair radiation or chemotherapy dosing. Efficacy of this combination is being explored further in this study and through larger phase III clinical trials. Clinical trial information: NCT02586207.

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Introduction Precision oncology (PO) is a growing treatment approach in the era of next-generation sequencing (NGS) and matched therapies. Effective delivery of PO in the community has not been extensively studied. Our program developed a virtual molecular tumor board (MTB) strategy to help guide PO care. Materials and Methods Over 18 months, eligible adult patients with advanced, incurable solid tumor malignancies were enrolled in a molecular profiling (MP) study using the Foundation Medicine NGS panel. Results were reviewed through a weekly, videoconferenced MTB conducted across our largely rural integrated health system. Recommendations from the MTB were used to identify actionable alterations (AAs). Feasibility of PO care delivery was assessed as the primary outcome. Secondary outcomes included the frequency of AAs, genomic matched treatments, genomic matched clinical trial enrollment, and clinical outcomes. Results A total of 120 participants with a variety of advanced tumor types were enrolled. Of these, 109 (90.8%) had successful MP. Treatment on the basis of an AA was recommended by the MTB in 58% of patients (63 of 109) who had a successful MP result. For those completing MP, treatments included enrollment in a genomic matched clinical trial (n = 16; 14.6%) and genomic matched treatment with a Food and Drug Administration–approved agent (n = 23; 21.1%). Response and survival data were similar regardless of the matched treatment option chosen. Conclusion A video-conferenced MTB-facilitated NGS testing and treatment delivery system was implemented in our integrated community oncology program. Continued use of this model aims to increase understanding of the impact of PO in this setting.

Sinonasal lymphoepithelial carcinoma (SLEC) is an extremely rare malignancy. We present a case of SLEC in a 77-year-old man who presented with nasal congestion and persistent sinusitis. Imaging revealed a large right nasal mass involving right paranasal sinuses along with bulky bilateral cervical lymphadenopathy. In addition, there was a fluorodeoxyglucose avid L1 vertebral lesion. Biopsy of nasal mass and cervical lymph nodes showed syncytial growth of tumor cells in a lymphoplasmacytic background. Immunohistochemical stains showed positivity for pankeratin, CK5/6, epithelial membrane antigen, p40 (focal), and p63 (focal). An Epstein-Barr virus-encoded RNA by in situ hybridization was strong and diffusely positive. Based on these pathologic findings and considering the location of tumor, diagnosis of SLEC was rendered. L1 vertebral body lesion was clinical and radiologically considered to be a metastasis. Correlation with radiology to determine the exact location of tumor is extremely important for correct diagnosis due to its histopathologic similarities with relatively more common undifferentiated type of nasopharyngeal carcinoma. No standard treatment protocol has been established for this tumor yet. To our knowledge, this is first ever report of SLEC presented with clinical stage IV disease.