Abstract A008: Imaging response to induction PD-1 and PARP inhibition in patients with locally advanced head and neck squamous cell carcinoma
Authors: Chen Xuguang S. , Shen Colette J. , Huang Benjamin Y. , Jewells Valerie L. , Repka Michael C. , Schrank Travis P. , Sullivan Christopher B. , Yarbrough Wendell G. , Hackman Trevor G. , Lumley Catherine , Blumberg Jeffrey M. , Patel Shetal A. , Trivedi Sumita , Weiss Jared , Chera Bhisham , Sheth Siddharth 
Published: January 2025

Abstract
Introduction: Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have high risk of disease progression and death after standard concurrent chemoradiotherapy (CCRT). We are conducting a prospective trial to investigate the efficacy of combining immune checkpoint blockade (ICB) with PARP inhibition prior to and following CCRT. Here we report the feasibility of utilizing pre- and post-induction CT simulations to assess early imaging response in patients treated on trial. Methods: NCT05366166 is an ongoing multi-institution, phase II trial. Patients with HPV negative or high-risk HPV positive LA-HNSCC were eligible. All received induction pembrolizumab 400mg IV and olaparib 150mg BID for 3 weeks followed by CCRT to 70Gy with weekly cisplatin (40mg/m2) followed by one year of maintenance pembrolizumab 400mg every 6 weeks and olaparib 150mg BID. Per protocol, all patients underwent CT simulation in the radiation treatment position with intravenous contrast pre- and post-induction. Dedicated post-induction imaging by radiology was not obtained. Gross tumor volumes of the primary (GTVp) and nodal (GTVn) disease were contoured on the pre- and post-induction simulation CTs by the treating physician in RayStation (RaySearch Laboratories). Pre- and post-induction simulation CTs were evaluated by two neuroradiologists independently using the RECIST criteria (v1.1). Statistical analyses were conducted in Microsoft Excel. Results: We evaluated the first 9 patients treated on-study at our center only. Median age was 67 years (range 59-76) and 78% were male. Location of primary site was oropharynx (N=6; 4 were HPV-positive), oral cavity (N=2), and larynx (N=1). 78% were T3-T4 and 89% had N2-N3 nodal disease. The median duration from the start of induction therapy to post-induction simulation was 22 days (range 7-51). Following induction, all patients experienced symptomatic benefit and had stable disease without progression per RECIST. Comparing pre- and post-induction GTVp and GTVn, overall mean volumes were not statistically different (mean±standard deviation -- 34.0±17.9 vs 35.6±19.5 cm3 for GTVp and 38.7±51.8 vs 39.5±54.2 cm3 for GTVn, respectively). At the individual patient level, the percent volume change after induction ranged from -21.9 to +16.5% (GTVp) and -48.7 to +53.2% (GTVn). Two patients (22%) had a decrease in GTVp, while five (56%) had a decrease in GTVn. There was a positive correlation (Pearson coefficient 0.77) between the percent volume changes in GTVp and GTVn (p=0.016). No differences in response by TNM stage or HPV status were observed. Conclusion: Favorable clinical and radiographic responses to three weeks of induction pembrolizumab and olaparib suggest anti-tumor activity. Performing pre- and post-induction radiation CT simulations is necessary to ensure adequate and accurate assessment of tumor extent for radiation planning. Therefore, omitting conventional post-induction scans by radiology to assess tumor response may be feasible. Formal cost-effective analysis will be conducted.
Citation Format: Xuguang S. Chen, Colette J. Shen, Benjamin Y. Huang, Valerie L. Jewells, Michael C. Repka, Travis P. Schrank, Christopher B. Sullivan, Wendell G. Yarbrough, Trevor G. Hackman, Catherine Lumley, Jeffrey M. Blumberg, Shetal A. Patel, Sumita Trivedi, Jared Weiss, Bhisham Chera, Siddharth Sheth. Imaging response to induction PD-1 and PARP inhibition in patients with locally advanced head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A008.