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251 Factors evaluated as predictors of exceptional response to PD-1 inhibitors in patients with head and neck squamous cell cancer
  1. Alexander Song,
  2. Ron Ng,
  3. John Heller,
  4. Robin Petro,
  5. Ralph D’Agostino,
  6. Thomas Lycan and
  7. Mercedes Porosnicu
  1. Wake Forest School of Medicine, Winston Salem, NC, USA


Background Immunotherapy has recently emerged as an alternative to traditional chemotherapy in the management of recurrent or metastatic head and neck squamous cell cancer (HNSCC). PD-1 inhibitors were approved for HNSCC in 2016 with ORR of 13–18% and CR of 4%.1, 2 Current research focuses on identifying predictors of response for better patient selection. We present HNSCC patients with exceptional response to PD-1 inhibitors in an attempt to highlight biomarkers that correlated with their remarkable response.

Methods We analyzed all cases of HNSCC treated with single agent PD-1 inhibitors in the last 4 years at Wake Forest Comprehensive Cancer Center. To identify exceptional responders, we followed the NIH Initiative definition: complete response to drug(s), where complete response is seen in less than 10% of patients receiving similar treatment or partial response lasting at least 6 months, where such response is seen in less than 10% of patients receiving similar treatment. We aimed to test all patients for PD-L1 expression, tumor genomics by Foundation Medicine platform and mutated circulating tumor DNA via Guardant 360 platform.

Results Based on the above criteria, 11 patients were identified as exceptional responders, 9 of whom had metastatic spread to lung, liver or bones. 7 patients were treated for more than one year, and all achieved CR. 3 patients were treated for less than one year, and all achieved major PR with possible CR to be confirmed with next scans. One patient with metastatic HNSCC achieved CR after just 3 administrations of PD-1 inhibitor and has been in CR for 3.5 years. 9 patients were tested for PD-L1 before starting immunotherapy, and all presented levels above 5% by TPS and above 10% by CPS. Interestingly, three patients older than 75 had the highest PD-L1: 75% by TPS and 100% by CPS in two patients. TMB was found moderate or high in all 8 patients tested before starting immunotherapy. TP53 was found mutated both in tumor and in blood in all but 2 of the 10 tested patients, one of whom is the only HPV positive patient in our series. MSI was stable in all patients.

Conclusions There are limited reports in the literature of exceptional responders to immunotherapy, particularly among HNSCC patients. High PD-L1 expression, moderate or high TMB and presence of mutated TP53 in both tumor and blood were present in almost all patients, recommending for further investigations as possible predictors of exceptional response to PD-1 inhibitors.

Ethics Approval The study was approved by Wake Forest University Institution’s Ethics Board, approval number IRB00056249.


  1. T.Y. Seiwert, B. Burtness, R. Mehra, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17(7):pp. 956–965.

  2. Ferris RL, Blumenschein GJr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856–67. 10.1056/NEJMoa1602252

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