Abstract PO-008: Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122
Authors: Chan Anthony T. C. , Lee Victor Ho Fun , Hong Ruey-Long , Ahn Myung-Ju , Chong Wan Qin , Spreafico Anna , Kim Sung-Bae , Ho Gwo Fuang , Caguioa Priscilla B. , Ngamphaiboon Nuttapong , Swaby Ramona F. , Wei Bo , Webber Andrea , Kang John , Gumuscu Burak , Yuan Jianda , Siu Lillian 
Published: September 2023

Abstract
Introduction: Plasma Epstein-Barr virus (EBV) DNA has been shown to be a sensitive and specific biomarker for prognosis, surveillance of recurrence, and treatment response of nasopharyngeal cancer (NPC). The phase 3 KEYNOTE-122 trial (NCT02611960) was conducted to evaluate pembrolizumab (pembro) vs standard of care (SOC) chemotherapy (chemo) in patients with platinum-pretreated recurrent/metastatic (R/M) NPC. This exploratory analysis was designed to evaluate association between plasma EBV DNA load and clinical response in patients treated with pembro or SOC in KEYNOTE-122. Materials and Methods: Patients who received ≥1 prior platinum-based chemo with histologically confirmed EBV-positive R/M NPC measurable per RECIST v1.1 and an ECOG PS ≤1, were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for ≤35 cycles or investigator’s choice of SOC chemo (capecitabine, gemcitabine, or docetaxel). Association between baseline plasma EBV DNA load, as measured using a high-sensitivity qPCR assay, and clinical outcomes (ORR, PFS, OS) was evaluated within each treatment arm. Significance of continuous EBV DNA load was prespecified at 0.05 for 1-sided P values from logistic (ORR) and Cox proportional hazard regression (PFS, OS) adjusted for ECOG PS. Additional assessments included association between clinical outcomes and plasma EBV DNA load fold change from baseline at cycle 2, day 1 (C2D1), after baseline adjustment, and descriptive comparison between baseline plasma EBV DNA load and tumor volume in predicting clinical outcomes. Clinical data cutoff: November 30, 2020. Results: 215/228 (94.3%) treated patients had evaluable plasma EBV DNA load data at baseline (pembro, 111; SOC, 104). Baseline plasma EBV DNA load (as a continuous variable) was significantly associated with PFS and OS for pembro and SOC (both P &lt; 0.005) but not ORR (P = 0.105, pembro; 0.473, SOC). Association between plasma EBV DNA load fold change from baseline at C2D1 and ORR, PFS, or OS was P ≤ 0.005 for both pembro and SOC. Baseline plasma EBV DNA load was numerically more predictive of OS and PFS than tumor volume for both pembro (C index [95% CI]: EBV DNA [OS: 0.71, 0.64-0.77; PFS: 0.67, 0.60-0.74] vs tumor volume [OS: 0.47, 0.41-0.54; PFS: 0.42, 0.35-0.49]) and SOC (EBV DNA [OS: 0.67, 0.60-0.73; PFS: 0.64, 0.56-0.71] vs tumor volume [OS: 0.58, 0.51-0.65; PFS: 0.54, 0.46-0.62]). Conclusions: In this post hoc exploratory analysis of KEYNOTE-122, higher baseline plasma EBV DNA load was negatively associated with PFS and OS in patients with NPC treated with pembro or SOC. Independent of baseline association, a larger decrease in plasma EBV DNA load at C2D1 relative to baseline was associated with improved clinical outcomes to both treatments. EBV DNA was more predictive of clinical outcomes than tumor volume. While definitive conclusions are limited, these findings provide additional support for plasma EBV DNA as a prognostic biomarker for NPC, which could guide treatment decisions.
Citation Format: Anthony T. C. Chan, Victor Ho Fun Lee, Ruey-Long Hong, Myung-Ju Ahn, Wan Qin Chong, Anna Spreafico, Sung-Bae Kim, Gwo Fuang Ho, Priscilla B. Caguioa, Nuttapong Ngamphaiboon, Ramona F. Swaby, Bo Wei, Andrea Webber, John Kang, Burak Gumuscu, Jianda Yuan, Lillian Siu. Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122 [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-008.