Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida.
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
Clin Cancer Res. 2022 Jun 1;28(11):2329-2338. doi: 10.1158/1078-0432.CCR-21-3849.
A phase II multi-institutional clinical trial was conducted to determine overall survival (OS) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with a combination of cetuximab and nivolumab.
Patients with R/M HNSCC were treated with cetuximab 500 mg/m2 i.v. on day 14 as a lead-in followed by cetuximab 500 mg/m2 i.v. and nivolumab 240 mg i.v. on day 1 and day 15 of each 28-day cycle. Expression of p16 and programmed cell death-ligand 1 (PD-L1) in archived tumors were determined. Tumor-tissue-modified human papillomavirus (TTMV) DNA was quantified in plasma.
Ninety-five patients were enrolled, and 88 patients were evaluable for OS with a median follow-up of 15.9 months. Median OS in the 45 patients who had prior therapy for R/M HNSCC (cohort A) was 11.4 months, with a 1 year OS 50% [90% confidence interval (CI), 0.43-0.57]. Median OS in the 43 patients who had no prior therapy (cohort B) was 20.2 months, with a 1-year OS 66% (90% CI, 0.59-0.71). In the combined cohorts, the p16-negative immunostaining was associated with higher response rate (RR; P = 0.02) but did not impact survival while higher PD-L1 combined positive score was associated with higher RR (P = 0.03) and longer OS (log-rank P = 0.04). In the p16-positive patients, lower median (1,230 copies/mL) TTMV DNA counts were associated with higher RR (P = 0.01) and longer OS compared with higher median (log-rank P = 0.05).
The combination of cetuximab and nivolumab is effective in patients with both previously treated and untreated R/M HNSCC and warrants further evaluation.
进行了一项多中心二期临床试验，以确定接受西妥昔单抗联合纳武利尤单抗治疗的复发性和/或转移性（R/M）头颈部鳞状细胞癌（HNSCC）患者的总生存期（OS）。
将 R/M HNSCC 患者先接受西妥昔单抗 500 mg/m2 静脉滴注（iv），每 14 天一次作为导入治疗，随后在每个 28 天周期的第 1 天和第 15 天，再给予西妥昔单抗 500 mg/m2 iv 和纳武利尤单抗 240 mg iv。对存档肿瘤进行 p16 和程序性死亡配体 1（PD-L1）表达检测。检测血浆中人乳头瘤病毒（HPV）组织修饰型 TTMV DNA 载量。
共纳入 95 例患者，其中 88 例患者的 OS 可评估，中位随访时间为 15.9 个月。在 45 例先前接受过 R/M HNSCC 治疗的患者（队列 A）中，中位 OS 为 11.4 个月，1 年 OS 率为 50%[90%置信区间（CI），0.43-0.57]。在 43 例未接受过治疗的患者（队列 B）中，中位 OS 为 20.2 个月，1 年 OS 率为 66%（90%CI，0.59-0.71）。在两个队列中，p16 阴性免疫组化与更高的缓解率（RR；P = 0.02）相关，但与生存无关，而较高的 PD-L1 联合阳性评分与更高的 RR（P = 0.03）和更长的 OS（对数秩 P = 0.04）相关。在 p16 阳性患者中，较低的中位 TTMV DNA 载量（1,230 拷贝/ml）与更高的 RR（P = 0.01）和更长的 OS 相关，与较高的中位 TTMV DNA 载量相比（对数秩 P = 0.05）。
西妥昔单抗联合纳武利尤单抗在既往治疗和未经治疗的 R/M HNSCC 患者中均具有疗效，值得进一步研究。
