Saba Nabil F, Wong Stuart J, Nasti Tahseen, McCook-Veal Ashley Alesia, McDonald Mark W, Stokes William A, Anderson Allyson M, Ekpenyong Asari, Rupji Manali, Abousaud Marin, Rudra Soumon, Bates James E, Remick Jill S, Joshi Nikhil P, Woody Neil M, Awan Musaddiq, Geiger Jessica L, Shreenivas Aditya, Samsa Julia, Ward Matthew Christopher, Schmitt Nicole C, Patel Mihir R, Higgins Kristin A, Teng Yong, Steuer Conor E, Shin Dong M, Liu Yuan, Ahmed Rafi, Koyfman Shlomo A
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia.
Winship Cancer Institute, Emory University, Atlanta, Georgia.
JAMA Oncol. 2024 Jul 1;10(7):896-904. doi: 10.1001/jamaoncol.2024.1143.
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).
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.
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.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT03521570.
调强放射治疗（IMRT）对非转移性复发性或第二原发性头颈部鳞状细胞癌（HNSCC）进行再照射，会导致无进展生存期（PFS）和总生存期（OS）较差。
研究纳武利尤单抗（已批准用于HNSCC患者的标准治疗药物）在IMRT再照射期间及之后的耐受性、PFS、OS以及患者报告的结局。
设计、设置和参与者：在这项多中心非随机2期单臂试验中，评估了符合递归划分分析1类和2类定义的复发性或第二原发性HNSCC患者的治疗结局。2018年7月11日至2021年8月12日期间，62例患者同意参与并接受筛查。2023年6月至12月对数据进行了评估。
在6至6.5周内，分30至33次每日剂量给予60至66 Gy的IMRT，并联合纳武利尤单抗，在IMRT前2周静脉注射240 mg，IMRT期间每2周静脉注射240 mg共5个周期，之后每4周静脉注射480 mg，纳武利尤单抗总疗程为52周。
主要终点是PFS。次要终点包括OS、毒性反应的发生率和类型，包括长期治疗相关毒性反应、患者报告的结局以及组织和血液生物标志物的相关性。
共筛查62例患者，51例可评估（中位[范围]年龄为62[56 - 67]岁；42例[82%]为男性；6例[12%]为p16 +疾病；38例[75%]接受了挽救性手术；36例[71%]进行了颈部清扫术）。中位随访24.5个月（95%CI，19.0 - 25.0），估计1年PFS为61.7%（95%CI，49.2% - 77.4%），单臂对数秩检验在1年时间范围内P = 0.002，拒绝了1年PFS率低于43.8%的原假设。最常见的3级或更高等级治疗相关不良事件（6例[12%]）是淋巴细胞减少，2例患者（4%）以及各1例患者（2%）分别出现结肠炎、腹泻、肌炎、恶心、粘膜炎和重症肌无力。癌症治疗功能评估通用版和癌症治疗功能评估头颈问卷的生活质量评分在所有时间点均保持稳定且一致。观察到一个假设生成趋势，即血液中PD1 +、KI67 +和CD4 + T细胞增加的患者，其PFS和OS有恶化趋势。
这项关于IMRT再照射治疗和纳武利尤单抗的多中心非随机2期试验表明，与历史对照相比，PFS有显著改善。该治疗耐受性良好，值得进一步评估。
ClinicalTrials.gov标识符：NCT03521570。
