Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma: A Nonrandomized Controlled Trial. JAMA Oncol 2024 Jul 01;10(7):896-904
Date
05/23/2024Pubmed ID
38780927Pubmed Central ID
PMC11117153DOI
10.1001/jamaoncol.2024.1143Scopus ID
2-s2.0-85194249090 (requires institutional sign-in at Scopus site)Abstract
IMPORTANCE: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS).
OBJECTIVE: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023.
INTERVENTION: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks.
MAIN OUTCOMES AND MEASURES: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers.
RESULTS: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed.
CONCLUSIONS AND RELEVANCE: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03521570.
Author List
Saba NF, Wong SJ, Nasti T, McCook-Veal AA, McDonald MW, Stokes WA, Anderson AM, Ekpenyong A, Rupji M, Abousaud M, Rudra S, Bates JE, Remick JS, Joshi NP, Woody NM, Awan M, Geiger JL, Shreenivas A, Samsa J, Ward MC, Schmitt NC, Patel MR, Higgins KA, Teng Y, Steuer CE, Shin DM, Liu Y, Ahmed R, Koyfman SAAuthors
Musaddiq J. Awan MD Associate Professor in the Radiation Oncology department at Medical College of WisconsinStuart J. Wong MD Center Director, Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAged
Antineoplastic Agents, Immunological
Female
Head and Neck Neoplasms
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Neoplasms, Second Primary
Radiotherapy, Intensity-Modulated
Re-Irradiation
