870P - Dynamic cfHPV DNA changes during induction chemotherapy as an early indicator of treatment responsiveness for locally advanced head and neck cancer patients

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.