Swallowing and quality-of-life outcomes of response adaptive de-escalated therapy following nivolumab-based induction for HPV+ oropharyngeal cancer.
Authors: Ari Rosenberg, Alexander T. Pearson, Aditya Juloori, John Cursio, Zhen Gooi, Elizabeth A. Blair, Tanguy Y. Seiwert, Jeffrey Chin, Ellen MacCracken, Evgeny Izumchenko, Nishant Agrawal, Daniel J. Haraf, Everett E. Vokes
Journal: Journal of Clinical Oncology (2022)

6011 Background: Despite the survival benefit of anti-PD1 therapy in recurrent/metastatic head and neck cancer, its role in locoregional disease remains undefined. Swallowing and quality of life (QoL) outcomes for patients with human papillomavirus associated (HPV+) oropharyngeal cancer (OPC) treated with de-intensified local therapy following anti-PD1 based induction is unknown. Here we report functional swallowing and QoL outcomes with response-adaptive de-escalation after induction chemoimmunotherapy in the context of a prospective investigator initiated trial, OPTIMA II. Methods: OPTIMA II enrolled locoregionally advanced HPV+ OPC. Treatment consisted of induction therapy with 3 cycles of nivolumab, nab-paclitaxel, and carboplatin, followed by risk and response de-escalated local therapy. High-risk (HR) included: T4, N2c-N3 (AJCC 7th edition), &gt; 20 pack year smoking history, or non-HPV16 subtype; All others were low-risk (LR). Single-modality de-escalation received radiation (RT) alone to 50 Gy or transoral robotic surgery, and was administered to LR with ≥50% post-induction shrinkage by RECIST. Intermediate-dose de-escalation received chemoradiation (CRT) to 45-50Gy and was administered to HR with ≥50% shrinkage or LR with &lt; 50% shrinkage. All others received regular-dose CRT to 70-75 Gy. Adjuvant nivolumab was administered for 6 months. Swallowing and QoL was assessed with the Rosenbek score and EORTC QLQ-C30 questionnaires, respectively. Higher values indicated greater degree of swallowing dysfunction and worse QoL, respectively. Results: Seventy-three eligible patients (pts) initiated treatment on protocol. Median age 61 (range 37-82). Primary site was tonsil in 70% and base of tongue in 29%. T3 or T4 primary tumor in 30%. De-escalated therapy was administered in 62 pts, of which 28 pts received single-modality and 34 pts received intermediate-dose. Rosenbek mean and standard deviation (SD) at baseline among single-modality, intermediate-dose, and regular-dose, was 1.3 (SD 0.6), 1.7 (SD 1.3), and 1.4 (SD 0.7), respectively. Rosenbek mean at 1 month following local therapy (n = 45) among single-modality, intermediate-dose, and regular-dose was 2.3 (SD 1.6), 3.8 (SD 2.5), and 4.7 (SD 2.1), respectively (p = 0.06). Feeding tube rates at the end of local therapy among single-modality, intermediate-dose, and regular-dose was 7%, 44%, and 75% respectively (p &lt; 0.01). QoL scores (n = 30) were worse among regular-dose as compared with de-escalated treatment for activities of daily living (p = 0.01), neuropathy (p = 0.01), and eating in social settings (p = 0.09). Conclusions: Response adaptive de-escalated treatment for HPV+ OPC following nivolumab/nab-paclitaxel/carboplatin induction is associated with improved swallowing function, reduced rates of enteral feeding, and an improvement in QoL across several domains. Clinical trial information: NCT03107182.