Moroco Annie E, Nunes Kathryn, Alnemri Angela, Bridgham Kelly, Llerena Pablo, Tuluc Madalina, Gargano Stacey, Zhan Tingting, Thal Arielle G, Cognetti David M, Curry Joseph M, Johnson Jennifer M, Luginbuhl Adam J
Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania.
JAMA Otolaryngol Head Neck Surg. 2025 Jul 31. doi: 10.1001/jamaoto.2025.1707.
Neoadjuvant immunotherapy shows promise in the treatment of head and neck squamous cell carcinoma (HNSCC). Pathologic treatment effect (pTE) is one way to assess response to treatment; however, the association of this response with survival outcomes is not yet clear. The current study sought to determine whether treatment response to neoadjuvant nivolumab, as measured by pTE, correlates with survival outcomes.
To determine whether patients with HNSCC with pathologic response to neoadjuvant nivolumab have improved survival outcomes.
DESIGN, SETTING, AND PARTICIPANTS: A cohort study performing a pooled analysis of 2 multi-institutional neoadjuvant clinical trials (NCT03238365, NCT03854032) enrolling patients from July 2017 to January 2022, was performed. Patients with resectable HNSCC enrolled in 1 of 2 clinical trials and treated with neoadjuvant immunotherapy and surgical resection were included in the analysis. Patients were followed up for a median (range) of 36 (4-72) months. Analysis took place on April 15, 2024.
Patients were treated with neoadjuvant nivolumab with or without the addition of immunomodulating medications (tadalafil or indoleamine 2,3 dioxygenase inhibitor).
Pooled analysis was performed to plot Kaplan-Meier 3-year survival outcomes for pTE responders and low or nonresponders. A pTE response threshold was determined using recursive partitioning analysis.
Seventy-nine patients were included in the analysis, of whom 40 (51%) had human papillomavirus (HPV)-negative disease. Recursive partitioning analysis identified a pTE threshold of 57%, which was used to define pathologic responders vs low or nonresponders. Pathologic responders with HPV-negative disease had significantly improved disease-free survival (100% for responders vs 66.8% for low or nonresponders; 95% CI, 46.1%-80.6%) and overall survival (100% for responders vs 73.3% for low or nonresponders; 95% CI, 53.4%-85.7%). In patients with HPV-positive disease, disease-free survival was high for both responders (90%; 95% CI, 47.3%-98.5%) and low or nonresponders (92.4%; 95% CI, 72.8%-98.1%).
This cohort study found that patients with HPV-negative disease who are deemed pathologic responders (pTE >57%) to neoadjuvant nivolumab may have improved survival outcomes compared with those who are low or nonresponders. Not only does this suggest a role for using pathologic response as a surrogate marker, but it further highlights the neoadjuvant strategy in HNSCC as associated with improved survival.
新辅助免疫疗法在头颈部鳞状细胞癌（HNSCC）的治疗中显示出前景。病理治疗效果（pTE）是评估治疗反应的一种方式；然而，这种反应与生存结果之间的关联尚不清楚。当前研究旨在确定通过pTE衡量的新辅助纳武利尤单抗治疗反应是否与生存结果相关。
确定对新辅助纳武利尤单抗有病理反应的HNSCC患者是否有更好的生存结果。
设计、设置和参与者：进行了一项队列研究，对2项多机构新辅助临床试验（NCT03238365、NCT03854032）进行汇总分析，这些试验在2017年7月至2022年1月期间招募患者。纳入分析的患者为入组2项临床试验之一、接受新辅助免疫疗法和手术切除的可切除HNSCC患者。对患者进行了中位（范围）36（4 - 72）个月的随访。分析于2024年4月15日进行。
患者接受新辅助纳武利尤单抗治疗，可加用或不加用免疫调节药物（他达拉非或吲哚胺2,3 - 双加氧酶抑制剂）。
进行汇总分析以绘制pTE反应者与低反应者或无反应者的Kaplan - Meier 3年生存结果图。使用递归划分分析确定pTE反应阈值。
79例患者纳入分析，其中40例（51%）患有人乳头瘤病毒（HPV）阴性疾病。递归划分分析确定pTE阈值为57%，用于定义病理反应者与低反应者或无反应者。HPV阴性疾病的病理反应者的无病生存率显著提高（反应者为100%，低反应者或无反应者为66.8%；95%置信区间，46.1% - 80.6%），总生存率也显著提高（反应者为100%，低反应者或无反应者为73.3%；95%置信区间，53.4% - 85.7%）。在HPV阳性疾病患者中，反应者（90%；95%置信区间，47.3% - 98.5%）和低反应者或无反应者（92.4%；95%置信区间，72.8% - 98.1%）的无病生存率均较高。
这项队列研究发现，与低反应者或无反应者相比，被认为对新辅助纳武利尤单抗有病理反应（pTE>57%）的HPV阴性疾病患者可能有更好的生存结果。这不仅表明将病理反应用作替代标志物的作用，还进一步凸显了HNSCC中的新辅助策略与生存改善相关。
