Abstract 870P
Background
Imaging response to induction chemotherapy (IC) has been used as a chemoradiation (CRT) de-intensification strategy in HPV-related head and neck cancer (HPV-HNC). However, radiographic response can be difficult to interpret and may lag biological response. We evaluate serial cell free HPV DNA (cfHPV DNA) levels during IC and CRT to determine a quantitative measure of early biologic response.
Methods
Patients with locally advanced, HPV-HNC receiving IC with 1-2 cycles of weekly platinum/taxane and definitive CRT were eligible. Peripheral blood was collected biweekly during IC, weekly during CRT, and at 3-4mo follow up visit. cfHPV DNA levels were measured with the Safe-SEQ HPV test from Sysmex Inostics, which is an NGS-based, CLIA-certified assay designed to sensitively detect and quantify HPV16 and HPV18 DNA in plasma.
Results
163 samples across 15 patients completing curative-intent treatment were processed. The primary tumors were oropharyngeal (OPX, n=11), sinonasal/nasopharyngeal (NPX, n=3), and laryngeal (n=1). Median follow up was 13.2 mo. We defined a subset of patients who had ≥95% reduction in baseline cfHPV DNA levels by day 22 of IC as “rapid responders”. This included 4 OPX and 1 NPX patients. All rapid responders had either T4 or N3 disease and three had >15 pack-year smoking history. Mean tumor volume change measured from pre-IC to post-IC CT imaging (median of 43 elapsed days) was a 71% reduction for rapid responders (range: 55% to 89% reduction) and a 32% reduction for non-rapid responders (range: 31% increase to 62% reduction). All rapid responders were alive and locoregionally controlled at 1 year follow up. In contrast, 50% of the non-rapid responders experienced in-field locoregional failure by this time-point, with two dying with disease. Each of the rapid responders completely cleared cfHPV DNA by the end of week 4 of CRT, but one rapid responder rebounded to a low detectable level (1.5 copies/mL) at 3.4mo post-treatment, followed by clinical detection of distant recurrence 10 months later.
Conclusions
cfHPV DNA kinetics after a short course of IC can provide an early, quantitative indication of favorable biology even for clinically high-risk, locally advanced HPV-HNC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Sysmex Inostics, Inc. with in-kind support.
Disclosure
Y. Cao: Non-Financial Interests, Non financial benefits, In-kind donation of assay: Sysmex Inostics, Inc. A.P. Kiess: Other, Research Grant: Merck. E. Gramiccioni, D. Schmitt, J. Swindell: Financial Interests, Personal, Full or part-time Employment: Sysmex Inostics, Inc. A. Starus: Financial Interests, Personal, Full or part-time Employment, Sr. Manager, Medical Affairs and Product Development: Sysmex Inostics, Inc. F.S. Jones: Financial Interests, Personal, Full or part-time Employment, Senior Director Medical Affairs & Product Development: Sysmex Inostics, Inc. H. Quon: Financial Interests, Personal, Ownership Interest, Co-Founder, Chief Medical Officer, Stock: Pistevo Decision; Financial Interests, Personal, Advisory Role, Consultant, Stock: Oncospace LLC; Financial Interests, Non financial benefits, In-kind donation of assay: Sysmex Inostics, Inc. T. Seiwert: Financial Interests, Research Funding: Bristol Myers Squibb, AstraZeneca, Genenetch, Cue; Financial Interests, Research Funding, Consultant, Honoraria: Nanobiotix; Financial Interests, Research Funding, Consultant, honoraria: Merck; Non-Financial Interests, Non financial benefits, In-kind donation of assay: Sysmex Inostics, Inc.. All other authors have declared no conflicts of interest.
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