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809 Phase 2 trial of neoadjuvant and adjuvant PD-1 checkpoint blockade in local-regionally advanced, resectable HNSCC indicates pathological response is associated with high disease-free survival
  1. Trisha Wise-Draper1,
  2. Shuchi Gulati1,
  3. Vinita Takiar1,
  4. Sarah Palackdharry1,
  5. Francis Worden2,
  6. Matthew Old3,
  7. John Kaczmar4,
  8. Neal Dunlap5,
  9. Benjamin Hinrichs1,
  10. Diana Bell6,
  11. Yash Patil1,
  12. Muhammad Kashif Riaz1,
  13. Layne Weatherford1,
  14. Aubrey Hamilton1,
  15. Sheena Lanverman1,
  16. Michelle Mierzwa2,
  17. Keith Casper2,
  18. Jonathan Mark7,
  19. Alice Tang1,
  20. Chad Zender1,
  21. Ann Gillenwater6,
  22. Mario Medvedovich8,
  23. J Jack Lee6,
  24. Roman Jandarov8 and
  25. Maura Gillison6
  1. 1University of Cincinnati Cancer Center, Cincinnati, OH, USA
  2. 2University of Michigan, Ann Arbor, MI, USA
  3. 3Ohio State University, Columbus, OH, USA
  4. 4MUSC, Charleston, SC, USA
  5. 5University of Louisville, Louisville, KY, USA
  6. 6MD Anderson, Houston, USA
  7. 7East Virginia medical school, Norfolk, VA, USA
  8. 8University of Cincinnati, Cincinnati, OH, USA


Background Patients with newly diagnosed, resected, head and neck squamous cell carcinoma (HNSCC) with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year disease free survival (DFS) of 65% and 69%, respectively.1 PD-1/PD-L1 immune checkpoint blockade has improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiation upregulates PD-L1.2 Therefore, we hypothesized that pre and post-operative administration of the PD-1 inhibitor pembrolizumab would improve 1-year DFS for patients with resectable, loco-regionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093).

Methods Eligible patients received pembrolizumab (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembrolizumab (q3 wks x 6 doses) was administered with weekly cisplatin (40mg/m2 X 6) and radiation (60-66Gy) for those with high-risk features and radiation alone for patients with intermediate-risk features. The primary endpoint was DFS, which was compared by log-rank test to historical controls (RTOG 9501). Evidence of pathological response to neoadjuvant pembrolizumab was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE) defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. Response was classified as none (NPR, <20%), partial (PPR, ≥20% and <90%) and major (MPR, ≥90%) pathological response. Gene expression analysis in paired tumor specimens was evaluated by Nanostring.

Results Sixty-six of 84 enrolled patients had received adjuvant pembrolizumab and therefore were evaluable for DFS at the time of interim analysis. Patient characteristics included: median age 59 (range of 27 – 76) years; 30% female; 85% oral cavity, 11% larynx, and 2% human papillomavirus negative oropharynx; 85% clinical T3/4 and 68% ≥2N; 41(51%) high-risk (positive margins, 49%; ECE, 80%). At a median follow-up of 16 months, 1-year DFS was 66% (95%CI 0.48-0.84) in the high-risk group (p=1) and 91% (95%CI 0.79-1) in the intermediate-risk group (versus 69% in RTOG 9501, p=0.05) (figure 1). Among 70 patients evaluable for pathological response, TE was scored as NPR in 40, PPR in 27, and MPR in 3 patients. Patients with pathological response that were also evaluable for DFS (PPR + MPR) had significantly improved 1-year DFS when compared with those with NPR (100% versus 57%, p=0.0033; HR = 0.18 [95%CI 0.05-0.64]) (figure 2). PPR/MPR was associated with robust macrophage infiltration via Nanostring.

Abstract 809 Figure 1

Disease Free Survival by Pathological RiskPatients were stratified by pathological risk and DFS was measured

Abstract 809 Figure 2

Disease Free Survival by Pathological ResponsePaired patient tissue was assessed for treatment effect (TE) and patients with greater than or equal to 20% TE were considered to have developed pathological response. Patients were stratified into responders and non-responders and DFS was determined.

Conclusions Neoadjuvant and adjuvant pembrolizumab led to high DFS in intermediate-risk, but not high-risk, resected HNSCC patients. Pathological response to neoadjuvant pembrolizumab was associated with high 1-year DFS.

Acknowledgements We’d like to acknowledge the UCCC clinical trials office for their hard work on this study as well as our patients. We’d also like to acknowledge Merck & Co, Inc as they partially funded the clinical trial.

Trial Registration NCT02641093

Ethics Approval This study was approved by the University of Cincinnati IRB with approval number 2015-6798


  1. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350(19):1937-1944. doi:10.1056/NEJMoa032646

  2. Oweida A, Lennon S, Calame D, et al. Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma. Oncoimmunology2017;6(10):e1356153. Published 2017 Aug 3. doi:10.1080/2162402X.2017.1356153

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