Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Clin Cancer Res. 2022 Feb 1;28(3):468-478. doi: 10.1158/1078-0432.CCR-21-2635. Epub 2021 Oct 19.
Surgery often represents the best chance for disease control in locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We investigated dual immune-checkpoint inhibition [anti-PD-1, nivolumab (N), and anti-KIR, lirilumab (L)] before and after salvage surgery to improve disease-free survival (DFS).
In this phase II study, patients received N (240 mg) + L (240 mg) 7 to 21 days before surgery, followed by six cycles of adjuvant N + L. Primary endpoint was 1-year DFS; secondary endpoints were safety, pre-op radiologic response, and overall survival (OS). Correlatives included tumor sequencing, PD-L1 scoring, and immunoprofiling.
Among 28 patients, the median age was 66, 86% were smokers; primary site: 9 oral cavity, 9 oropharynx, and 10 larynx/hypopharynx; 96% had prior radiation. There were no delays to surgery. Grade 3+ adverse events: 11%. At the time of surgery, 96% had stable disease radiologically, one had progression. Pathologic response to N + L was observed in 43% (12/28): 4/28 (14%) major (tumor viability, TV ≤ 10%) and 8/28 (29%) partial (TV ≤ 50%). PD-L1 combined positive score (CPS) at surgery was similar regardless of pathologic response ( = 0.71). Thirteen (46%) recurred (loco-regional = 10, distant = 3). Five of 28 (18%) had positive margins, 4 later recurred. At median follow-up of 22.8 months, 1-year DFS was 55.2% (95% CI, 34.8-71.7) and 1-year OS was 85.7% (95% CI, 66.3-94.4). Two-year DFS and OS were 64% and 80% among pathologic responders.
(Neo)adjuvant N + L was well tolerated, with a 43% pathologic response rate. We observed favorable DFS and excellent 2-year OS among high-risk, previously treated patients exhibiting a pathologic response. Further evaluation of this strategy is warranted..
手术通常是局部复发性头颈部鳞状细胞癌（SCCHN）疾病控制的最佳机会。我们研究了在挽救性手术前后双重免疫检查点抑制[抗 PD-1、nivolumab（N）和抗 KIR、lirilumab（L）]以改善无病生存（DFS）。
在这项 II 期研究中，患者在手术前 7 至 21 天接受 N（240mg）+L（240mg）治疗，然后接受六周期辅助 N+L 治疗。主要终点是 1 年 DFS；次要终点是安全性、术前影像学反应和总生存（OS）。相关性包括肿瘤测序、PD-L1 评分和免疫分析。
在 28 例患者中，中位年龄为 66 岁，86%为吸烟者；原发部位：9 例口腔，9 例口咽，10 例喉/下咽；96%有既往放疗史。手术没有延误。3 级以上不良事件：11%。在手术时，96%的患者影像学上疾病稳定，1 例进展。N+L 的病理反应观察到 43%（28/28）：4/28（14%）主要（肿瘤存活，TV≤10%）和 8/28（29%）部分（TV≤50%）。手术时的 PD-L1 联合阳性评分（CPS）与病理反应无关（=0.71）。13 例（46%）复发（局部=10，远处=3）。28 例中有 5 例（18%）切缘阳性，4 例随后复发。在 22.8 个月的中位随访中，1 年 DFS 为 55.2%（95%CI，34.8-71.7），1 年 OS 为 85.7%（95%CI，66.3-94.4）。病理反应者的 2 年 DFS 和 OS 分别为 64%和 80%。
（新）辅助 N+L 耐受性良好，病理反应率为 43%。我们观察到在高危、既往治疗的患者中，DFS 结果良好，2 年 OS 优异，且表现出病理反应。需要进一步评估这种策略。
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