Abstract 1112: Feasibility of real-time personalized patient-derived Tumorgraft® models for guiding systemic treatment in recurrent and/or metastatic head and neck cancer patients
Authors: Morgan D. Black, Allison Berger, Nicole Pinto, John Yoo, Kevin Fung, Danielle MacNeil, David A. Palma, Joseph S. Mymryk, Sara Kuruvilla, John W. Barrett, Suzanne Richter, Angela Davies, Eric W. Winquist, Anthony C. Nichols
Journal: Cancer Research (2020)

Abstract Background: Recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC) is associated with poor quality of life and a poor prognosis with a median overall survival of 7 months. With limited systemic therapy options, there is an urgent need to identify predictive biomarkers for drug response. Patient derived xenografts (PDXs) have been demonstrated to preserve the histological features, heterogeneity, epigenetic and genetic profiles of the original tumor and appear to correlate well with objective tumor response in patients. This study aimed to test the feasibility of personalized PDXs for guiding systemic treatment in RMHNSCC. Methods: Eligible patients were consented and a fresh biopsy/surgical sample was obtained and implanted into mice (5-15 mice/patient) to establish TumorGraft® models. Engrafted tumors were excised and propagated into second generation models for drug testing with up to 4 drugs selected by the treating medical oncologist. Tumor dimensions were measured twice weekly and were reported as one of: progressive disease, stable disease (SD), partial response (PR), or complete response (CR) based on the percentage of tumor regression. Patients alive and suitable for chemotherapy were prescribed the regimen(s) observed to have the greatest response rate in their TumorGraft® models. Patients' responses to therapy were then observed. Results: Nine of 10 eligible patients had samples successfully engrafted with an average time to engraftment of 89.2 days (± SD 41.7 days). Drug testing was not performed on 5 patients as the patient either died or was not suitable for treatment. The remaining 4 patient TumorGraft® models underwent drug testing with the average time from engraftment completion to drug testing completion being 83.8 ± 59.9 days. Two of these patients then received xenograft-guided therapy. In one patient, paclitaxel demonstrated a partial response in the Tumorgraft®, however the patient's tumor did not respond and their clinical status rapidly deteriorated leading to death. In the second patient, cetuximab and paclitaxel demonstrated the best response in the TumorGraft® model. This patient had a sequential partial response to each drug including a 17 month response to cetuximab before progressing and transitioning to nivolumab. The patient remains alive with stable disease 3.5 years after diagnosis of recurrent disease. Conclusions: The main limitation of Tumorgraft® testing for this population is the time delay to obtain Tumorgraft® results. Despite this, Tumorgraft® testing is feasible for a subset of patients and appears to correlate with clinical benefit. Citation Format: Morgan D. Black, Allison Berger, Nicole Pinto, John Yoo, Kevin Fung, Danielle MacNeil, David A. Palma, Joseph S. Mymryk, Sara Kuruvilla, John W. Barrett, Suzanne Richter, Angela Davies, Eric W. Winquist, Anthony C. Nichols. Feasibility of real-time personalized patient-derived Tumorgraft® models for guiding systemic treatment in recurrent and/or metastatic head and neck cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1112.