Prospective Phase II Trial of Definitive Chemoradiation and Concurrent Nivolumab in Locally Advanced p16+ Oropharynx Cancer

Prospective Phase II Trial of Definitive Chemoradiation and Concurrent Nivolumab in Locally Advanced p16+ Oropharynx Cancer

Purpose: We conducted a prospective, single-institution phase II trial to test the hypothesis that the addition of nivolumab to definitive chemoradiation would improve the progression-free survival (PFS) among patients with high-risk p16+ oropharyngeal squamous cell carcinoma (OPSCC). Methods and Ma...

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Main Authors: Samuel Nicholas Regan, MD, Jennifer Shah, MD, Krithika Suresh, PhD, Krystal A. Morales, MD, PhD, Yue Cao, PhD, Madhava Aryal, PhD, Benjamin S. Rosen, PhD, Heather Walline, PhD, Choonik Lee, PhD, Jessica Aldous, BS, Paul L. Swiecicki, MD, Keith A. Casper, MD, Steven B. Chinn, MD, Kelly M. Malloy, MD, Mark E.P. Prince, MD, Chaz L. Stucken, MD, Andrew G. Shuman, MD, Molly Heft-Neal, MD, Teresa H. Lyden, MA, CCC-SLP, Anna Blakely, MA, CCC-SLP, Madison Ambrose, MA, CCC-SLP, John Chad Brenner, PhD, Francis P. Worden, MD, Michelle L. Mierzwa, MD
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Advances in Radiation Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S2452109425001198
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Summary:Purpose: We conducted a prospective, single-institution phase II trial to test the hypothesis that the addition of nivolumab to definitive chemoradiation would improve the progression-free survival (PFS) among patients with high-risk p16+ oropharyngeal squamous cell carcinoma (OPSCC). Methods and Materials: Patients with previously-untreated locoregionally advanced, p16+ OPSCC (clinical T4/N3, matted lymph nodes, and/or retropharyngeal lymphadenopathy) were enrolled. Patients received a priming dose of nivolumab, concurrent nivolumab and chemoradiation (70 Gy to PTVhigh, 56 Gy to PTVlow, weekly carboplatin/paclitaxel), and 4 cycles of adjuvant nivolumab over 12 weeks. The primary endpoint was 2-year PFS compared to an institutional historic control of 68%. Exploratory endpoints included associations between survival and circulating tumor DNA kinetics during treatment and pretreatment/midtreatment 18F-fluorodeoxyglucose positron-emission tomography with computed tomography and magnetic resonance imaging metrics (gross tumor volume, low blood volume tumor subvolume, low apparent diffusion coefficient tumor subvolume, and metabolic tumor volume ≥50% of maximum standardized uptake value). Results: Twenty-six patients were enrolled prior to an interim analysis; 65% cT4, 46% with matted nodes, with a median total gross tumor volume of 60 cc (range, 36-165). Estimated 2-year PFS was 65% (2-sided 90% CI, 46%-79%) and 2-year distant metastasis-free survival was 84% (66%-93%). The majority (69%) did not complete the full course of nivolumab because of toxicity, and 54% experienced grade ≥3 acute dysphagia. Statistical analyses showed that increasing values of imaging-defined primary tumor subvolumes were significant associated with inferior PFS (eg, midtreatment low apparent diffusion coefficient: HR, 5.61; P = .05) and distant metastasis-free survival (eg, pretreatment metabolic tumor volume ≥50% of maximum standardized uptake value: HR, 2.97; P = .05). Midtreatment circulating tumor DNA kinetics were not associated with survival endpoints. Conclusions: Concurrent and adjuvant nivolumab did not improve PFS in locoregionally advanced Human papillomavirus+ OPSCC and was associated with significant toxicity. Physiological magnetic resonance imaging and 18F-fluorodeoxyglucose positron-emission tomography with computed tomography imaging markers are potential biomarkers to guide future therapy escalation strategies in high-risk oropharynx cancer.
ISSN:2452-1094

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