Oppelt Peter J, Ley Jessica C, Puram Sidharth V, Jackson Ryan S, Paniello Randall C, Rich Jason T, Pipkorn Patrik, Liu Jingxia, Thorstad Wade L, Adkins Douglas R
Division of Medical Oncology, Washington University School of Medicine, St Louis, MO.
Alvin J. Siteman Cancer Center, St Louis, MO.
JCO Precis Oncol. 2025 May;9:e2500069. doi: 10.1200/PO-25-00069. Epub 2025 May 22.
The primary aim of this single-arm, phase II trial was to determine the objective response rate (ORR) with palbociclib, a selective CDK4/6 inhibitor, administered before chemoradiotherapy (CRT) in patients with human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC).
Eligibility required untreated stage III-IVB HPV-negative HNSCC. Palbociclib 125 mg once daily was administered on days 1-21 of each 28-day cycle for two cycles before and six cycles after CRT. Pretreatment tumor samples underwent genome sequencing. The primary end point was tumor response to palbociclib given before CRT, assessed by RECIST1.1. A sample of 24 evaluable patients (those with response assessment) yielded an 80% power at a one-sided significance level of 0.05 if the ORR was ≥38% (null ORR 17%). A key secondary end point was relapse.
We enrolled 26 patients with HPV-negative, locally advanced HNSCC. Alterations in were identified in 15 patients (58%), and alterations in were identified in eight (31%). Twenty-four patients were evaluable for the primary end point, and 25 were evaluable for relapse. The ORR with palbociclib given before CRT was 41.7% (95% CI, 22.1 to 63.4). Response to palbociclib occurred in 10 of 15 patients (66.7%) with versus 0 of 9 (0%) without tumor alterations ( = .002) and in one of six patients (16.7%) with versus nine of 18 (50%) without alterations ( = .34). The median follow-up was 33.9 months (IQR, 31.3-49.2). Relapse occurred in two of 15 patients (13.3%) with versus seven of 10 (70%) without tumor alterations ( = .009) and in one of seven patients (14.3%) with versus 8 of 18 (44.4%) without alterations ( = .36).
Palbociclib is an active drug in previously untreated HPV-negative, locally advanced HNSCC. Alterations in were associated with a higher ORR with palbociclib and a lower relapse risk after CRT.
本单臂II期试验的主要目的是确定在人乳头瘤病毒（HPV）阴性的头颈部鳞状细胞癌（HNSCC）患者中，在放化疗（CRT）前给予选择性细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂帕博西尼的客观缓解率（ORR）。
入选标准为未经治疗的III-IVB期HPV阴性HNSCC。在每个28天周期的第1-21天，每天一次给予帕博西尼125mg，在CRT前给药两个周期，CRT后给药六个周期。治疗前的肿瘤样本进行基因组测序。主要终点是CRT前给予帕博西尼后的肿瘤反应，采用RECIST1.1进行评估。如果ORR≥38%（无效ORR为17%），24例可评估患者（有反应评估的患者）在单侧显著性水平为0.05时具有80%的检验效能。一个关键的次要终点是复发。
我们纳入了26例HPV阴性、局部晚期HNSCC患者。15例患者（58%）检测到[此处原文缺失相关基因名称]改变，8例患者（31%）检测到[此处原文缺失相关基因名称]改变。24例患者可评估主要终点，25例患者可评估复发情况。CRT前给予帕博西尼的ORR为41.7%（95%CI，22.1至63.4）。15例有[此处原文缺失相关基因名称]改变的患者中有10例（66.7%）对帕博西尼有反应，而9例无该肿瘤改变的患者中无1例有反应（P = 0.002）；6例有[此处原文缺失相关基因名称]改变的患者中有1例（16.7%）有反应，而18例无该改变的患者中有9例（50%）有反应（P = 0.34）。中位随访时间为33.9个月（IQR，31.3 - 49.2）。有[此处原文缺失相关基因名称]改变的15例患者中有2例（13.3%）复发，而10例无肿瘤改变的患者中有7例（70%）复发（P = 0.009）；有[此处原文缺失相关基因名称]改变的7例患者中有1例（14.3%）复发，而18例无该改变的患者中有8例（44.4%）复发（P = 0.36）。
帕博西尼在先前未经治疗的HPV阴性、局部晚期HNSCC中是一种活性药物。[此处原文缺失相关基因名称]改变与帕博西尼治疗后较高的ORR和较低的CRT后复发风险相关。
