CA209-9KY: Results of a phase II study of intensity modulated radiotherapy (IMRT) re-irradiation and concurrent/adjuvant nivolumab (nivo) in patients with loco-regionally recurrent or second primary (RSPT) head and neck squamous cell carcinoma (HNSCC).
Authors: Nabil F. Saba, Mark William McDonald, Ashley McCook-Veal, William A. Stokes, Tahseen Nasti, Soumon Rudra, James Edward Bates, Jill Remick, Nikhil Joshi, Neil McIver Woody, Jessica Lyn Geiger, Musaddiq Awan, Aditya V. Shreenivas, Kristin Ann Higgins, Conor Ernst Steuer, Rafi Ahmed, Dong Moon Shin, Yuan Liu, Stuart J. Wong, Shlomo A. Koyfman
Journal: Journal of Clinical Oncology (2022)

6029 Background: RSPT HNSCC within a previously irradiated field presents a technical challenge portending worse outcome. Anti-PD-1 therapy is an approved standard of care in the treatment of advanced HNSCC. CA209-9KY aimed to investigate the progression-free survival (PFS), tolerability, overall survival (OS) and patient reported outcomes (PRO) of nivo during and after IMRT re-irradiation. We report here the results for 51 enrolled and evaluable patients Methods: Following IRB approval at 3 participating institutions (Emory University, Cleveland Clinic, Medical College of Wisconsin), patients (pts) were enrolled if they had RSPT in a previously irradiated field (&gt;40Gy) and met criteria for recursive partition analysis (RPA) classes I or II (Ward et al, IJROBP 2018). Salvage resection was allowed provided the presence of pos margins, ENE, pN2/3 or pT3/4 disease, multifocal PNI, or LVI. IMRT re-irradiation to a total of 60-66 Gy in 30-33 daily fractions were delivered over 6-6.5 weeks with nivo (240 mg) two weeks prior and every 2 weeks x 5 during IMRT then at 480 mg every 4 weeks up to 52 weeks. The primary endpoint was improvement in 1-yr PFS from 40% to 55% (one-sided alpha of 0.05 and an 85% power). Results: As of 1/2022, a total of 51 evaluable pts completed IMRT with nivo. Median age 62 (56-67), RPA status 1 (23, 46%), 2 (27, 54%), Males (41, 80%), ECOG performance status 0 (13, 25%) 1 (36, 71%), 2 (2, 4%); p16 pos (16, 31%), neg (9,18%), not applicable (26, 51%). With a median follow up of 12.5 mos (11.2-14.0) the 1- yr PFS was 57.8% (95% CI, 41.3-71.1%) and OS was 81.7% (95% CI, 65.2-90.9%). Among 38 pts with available flow cytometry, pts with a 1.5-fold increase in peripheral blood PD1+KI67+CD8+ T cells (baseline to weeks 2 or 4) had an OS of 19.3 mos (vs 13.3 mos) (p=0.1617). Adverse events (AEs) (CTCAE version 4.0) included fatigue(40, 78%), dermatitis (30,58%), dysphagia (28, 54%). Most frequent serious AEs were anorexia and dyspnea (2, 4% each). Treatment related &gt;3 AEs were lymphopenia (2, 4%), colitis, diarrhea, mucositis and nausea (1, 2% each). FACT-G and FACT-H&amp;N QOL scores remained stable and consistent across all time points (52 weeks) (Cronbach’s alpha of &gt; 0.7) (ASTRO 21, abstract # 2738). Conclusions: CA209-9KY met its primary endpoint of 1-yr PFS; IMRT reirradiation with concurrent and adjuvant nivo is clinically effective, well tolerated and deserves further exploration in patients with RSPT HNSCC. CA209-9KY was supported by a grant from BMS. Clinical trial information: NCT03521570.