Abstract 3205: Superiority of response to carboplatin vs cisplatin in combination with pembrolizumab for head and neck squamous cell carcinoma predicted using ex vivo platform, CANscript
Authors: Kapoor Vidushi , Smalley Munisha , Verma Amit , Thyiagarajan Saravanan , Majumder Biswanath , Basak Nandini , Basu Abhishek , Kar Pradeep , Sabitha K.s. , Doval D.C. , Goldman Aaron J. 
Published: August 2019

Abstract
Background: Immunotherapy is a developing paradigm in the treatment of head and neck squamous cell carcinoma (HNSCC). An ongoing clinical trial (KEYNOTE-048) examines the efficacy of combining a PD-1 checkpoint inhibitor (pembrolizumab) with carboplatin or cisplatin (pt) and 5-fluorouricil (5-FU) vs. 5-FU+pt+cetuximab (EXTREME). Early evidence from this trial suggests overall survival is improved with the combination of pembrolizumab compared to EXTREME. However, no evidence has yet been reported around carboplatin vs. cisplatin in these regimens.
Methods: Here, with informed consent under IRB, fresh tumor biopsies were obtained from a randomly-selected cohort of HNSCC patients diagnosed with metastatic or locally advanced disease (N=45). We then employed CANscriptTM, a clinically-validated ex-vivo tumor platform that can predict clinical efficacy of agents using a proprietary algorithm, termed M-Score. The following regimens were tested in CANscript: (i) pembrolizumab as single agent, (ii) combination of pembrolizumab + Pt + 5-FU and (iii) cetuximab + Pt + 5-FU regimen. Importantly, Pt was run as either carboplatin or cisplatin in the combination regimens. In addition, PDL-1, CD4 and CD8 status was quantified for every patient by immunohistochemistry.
Results: Consistent with the recently reported data from KEYNOTE-048, we predicted, based on M-Score, that single agent pembrolizumab is inferior to either EXTREME or the pembrolizumab chemotherapy combination regimens. Interestingly, however, when samples were analyzed based on the type of platinum used (Carboplatin vs. Cisplatin) we determined that greater clinical response is achieved with the combination of Pembro/Carbo/5-FU (45.5% or 10/22) vs. Pembro/Cis/5-FU (21.7% or 5/23). In contrast, we predicted EXTREME regimen alone results in similar response rates regardless of the addition of Carbo or Cis (31.8% vs. 30.4%, respectively). Upon further interrogation we observed changes in immunohistochemical staining of PD-L1, CD8 and CD4 before vs. after treatment with either Cis or Carbo, but did not find a correlation between PD-L1 status at baseline with response. In addition, we found unique patterns of immunological response in the carbo vs. cis arms, which may explain why pembrolizumab performed better.
Conclusions: These results demonstrate the utility and highlight the ability of CANscript system to profile clinical response of immunotherapy. More importantly, our evidence that discrete differences exist between carboplatin and cisplatin could help future design of combination chemotherapy-immunotherapy regimens.
Citation Format: Vidushi Kapoor, Munisha Smalley, Amit Verma, Saravanan Thyiagarajan, Biswanath Majumder, Nandini Basak, Abhishek Basu, Pradeep Kar, K.s. Sabitha, D.C. Doval, Aaron J. Goldman. Superiority of response to carboplatin vs cisplatin in combination with pembrolizumab for head and neck squamous cell carcinoma predicted using ex vivo platform, CANscript [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3205.