Abstract 911P
Background
Detectable plasma EBV DNA post-RT portends for a poor prognosis in NPC patients. Adjuvant chemotherapy (AC) trials however failed to yield a survival benefit in these high-risk patients. Studies have shown that post-RT EBV DNA levels and kinetics could further stratify NPC patients into risk-groups with disparate survival. There is thus a need to correctly identify patients who benefit from AC. Here, we investigated whether an early (0-2 w) or delayed (8-12 w) measure of plasma EBV DNA better predicts for disease relapse.
Methods
We curated a prospective single institution NPC registry for patients with a plasma EBV DNA result at 0-2 w post-RT and a minimum follow-up of 2 years. A subset of patients had a duplicate test done at 8-12 w post-RT. Plasma EBV DNA was quantified using the international harmonised BamH1 PCR-based assay. Primary clinical endpoint was disease-free survival (DFS).
Results
297 patients with an EBV DNA result at 0-2 w post-RT were analysed. Median follow up was 51 (IQR: 47-55) mo. 71% (210/297) had TNM-stage III-IVA NPC; and 41% (122/297) reported pre-RT EBV DNA of ≥4000 copies/mL. At 0-2 w post-RT, 82% (243/297) had 0 EBV DNA copy/mL, while 16% (14/297) and 2% (7/297) had 1-264 copies/mL and ≥265 copies/mL, respectively. Using different EBV DNA level cut-offs of 0, 1-499, and ≥500 copies/mL, we validated the RPA model by Hui et al. with the high-risk group (≥500 copies/mL) yielding the worst HR of 4.9 (95%CI: 1.9-12.5) relative to the low-risk group. Next, we observed substantial EBV DNA changes in 109 patients with a repeat EBV DNA at 8-12 w. Specifically, 65% (22/34) with a detectable EBV DNA at 0-2 w had 0 copy/mL subsequently. We found that a detectable EBV DNA at 8-12 w was a stronger predictor of relapse than a positive result at 0-2 w; AUCROC for DFS was 0.806 (95%CI: 0.727-0.886) for stage+EBV DNA8-12w versus 0.679 (95% CI: 0.576-0.783) for stage+EBV DNA0-2w.
Conclusions
Our findings revealed that post-RT EBV DNA levels are dynamic, and an EBV DNA test at 8-12 w more accurately identifies high-risk patients than a test at 0-2 w post-RT. This has potential implications on AC trials that adopt an early EBV DNA result for treatment stratification.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Nasopharyngeal Cancer- Large Collaborative Grant (NPC-LCG), National Medical Research Council (NMRC), National Cancer Centre (NCC) Cancer Fund, Goh and Kua Hong Pak Foundation.
Disclosure
Y.L. Soong: Financial Interests, Personal, Stocks/Shares: GSK. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Steering Committee Member: Novartis. D.W. Lim: Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Institutional, Advisory Board: MSD, Roche, BeiGene; Financial Interests, Institutional, Trial Chair, Grant funding for investigator-sponsored study: Bristol Myers Squibb; Financial Interests, Institutional, Steering Committee Member: Novartis. M.L.K. Chua: Financial Interests, Institutional, Invited Speaker: Varian, AstraZeneca, Janssen, Pfizer, MSD; Financial Interests, Personal, Stocks/Shares: Digital Life Line; Financial Interests, Institutional, Other, Research agreement: Decipher Biosciences; Non-Financial Interests, Leadership Role: Head and Neck Cancer International Group. All other authors have declared no conflicts of interest.
Resources from the same session
932P - Survival in patients with relapsed/metastatic head and neck squamous cell carcinoma (HNSCC) treated with pembrolizumab or cetuximab-based therapy: A real-worlddata study with the TriNetX platform
Presenter: Lisardo Ugidos De La Varga
Session: Poster session 12
934P - Antitumor activity and safety profile of camrelizumab plus docetaxel, cisplatin, and capecitabine for induction therapy in advanced stage hypopharyngeal carcinoma
Presenter: Hongli Gong
Session: Poster session 12
938P - Nivolumab (nivo) in recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN): real-world effectiveness, quality of life (QoL) of patients and their caregivers in France (ProNiHN study)
Presenter: Christophe Le Tourneau
Session: Poster session 12
939P - Efficacy and safety of a novel anti-EGFR ADC MRG003 in recurrent or metastatic squamous cell carcinoma of the head and neck patients
Presenter: Liqiong Xue
Session: Poster session 12
940P - Salvage chemotherapy after progression on nivolumab in patients with squamous cell carcinoma of the head and neck included in the phase II TOPNIVO trial
Presenter: Khalil Saleh
Session: Poster session 12
941P - Risk factors for progressive disease after immune checkpoint inhibitors (ICIs) in advanced head and neck squamous cell carcinoma (HNSCC): Who might not be candidate for ICI?
Presenter: Seo Yoon Jang
Session: Poster session 12