CA209-9KY: Phase II Study of IMRT Re-Irradiation and Concurrent/Adjuvant Nivolumab (Nivo) in Patients With Loco Regionally Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma (HNSCC) - Toxicity and Quality of Life (QoL) Results.

Purpose/Objective(s) Approximately 30-40% of patients irradiated for HNSCC will develop locoregional recurrence or second primary tumors (RSPT). Treatment of RSPT originating within a previously radiated field presents a technical challenge and typically portends worse outcomes than an initial course of RT. Anti-PD-1 therapy has shown promise in the treatment of advanced HNSCC. CA209-9KY aimed to investigate the potential benefit of nivo during and after IMRT based re-irradiation in RSPT. We report here the toxicity and QOL data for 44 enrolled patients. Materials/Methods Following IRB approval at 3 participating institutions, patients were enrolled if they had RSPT arising in a previously irradiated field (> 40 Gy) and met criteria for reirradiation classes I or II (Ward et al, IJROBP 2018); prior salvage resection was allowed regardless of HPV status provided patients had positive margins, extranodal extension, gross residual disease, N2/3 or T3/4 disease, multifocal perineural invasion, and/or lymphovascular space invasion. IMRT reirradiation with photons was delivered in 60-66 Gy in 30-33 daily fractions over 6-6.5 weeks with Nivo (240 mg) two weeks prior to and every 2 weeks during IMRT for a total of 5 doses then at 480 mg every 4 weeks for a total of 52 weeks. The Functional Assessment of Cancer Therapy (FACT-G) (Version 4) was assessed pre-therapy and weeks 6, 18, 30 and 52. The sum of FACT-G subscales (SUMQOL) score was also computed. Median and interquartile range (IQR) for each subscale and SUMQOL were recorded per cycle visit. FACT-HN was assessed at the same time intervals. Internal consistency reliability was measured using Cronbach's alpha and reported for each FACT sub-scale at each cycle Results As of 1/2021, a total of 44 patients have completed IMRT with nivolumab with a median follow up duration of 6.3 mos [95% CI (4.5-11.2)]. The most common toxicities of any grade-(CTCAE version 4.0) were fatigue (77%), dermatitis (54%), and dysphagia (52%). Grade 3 or 4 toxicities occurred in 47% of patients, with lymphopenia being the most common (11%), followed by diarrhea (7%). Serious Adverse Event (SAEs) occurred in 20% of patients with the most reported being dyspnea (4%). The median total sumQoL scores for FACT-HN per visit were 71 (61-80), 73 (67-77), 70 (67.8-76.2), 74 (66.2-79.7) and 71 (66-79), respectively. Similar observations were seen for FACT-G Scores for subscales with a median total FACT-G sumQoL scores per visit 54 (46.2-56.8), 55(53.5-59.2), 54 (50-57), 55.5(52-58.2), and 55 (52.5-57.5), respectively. FACT-G and FACT-H&N QOL scores remained consistent across all time points analyzed. The internal consistency and reliability for the FACT scores per sub-scale, per cycle and for all response items had a Cronbach's alpha of > 0.7. Conclusion Reirradiation with IMRT with concurrent and adjuvant nivo in patients with RSPT appears to be well tolerated with preservation of QOL measures during and following completion of therapy. Follow up for clinical efficacy measures of IMRT-nivo continues.