Department of Medicine, Stanford Cancer Institute, Stanford, USA.
Drug Development Department, Gustave Roussy, Villejuif, France.
Ann Oncol. 2018 Nov 1;29(11):2247-2253. doi: 10.1093/annonc/mdy411.
Head and neck cancer (HNC) has a poor prognosis at advanced stages. Given the immunosuppressive tumor microenvironment in HNC, inhibition of the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling pathway represents a promising therapeutic approach. Atezolizumab (anti-PD-L1) is efficacious against many tumor types. Here we report the clinical safety and activity from the HNC cohort of the phase Ia PCD4989g clinical trial.
Patients with previously treated, advanced HNC received atezolizumab i.v. every 3 weeks for 16 cycles, up to 1 year or until loss of clinical benefit. Patients were monitored for safety and tolerability and evaluated for response at least every 6 weeks. Baseline PD-L1 expression level and human papillomavirus (HPV) status were evaluated.
Thirty-two patients were enrolled; 7 patients (22%) had a primary tumor in the oral cavity, 18 (56%) in the oropharynx, 1 (3%) in the hypopharynx, 2 (6%) in the larynx, and 4 (13%) in the nasopharynx. Seventeen patients (53%) had ≥2 prior lines of therapy. Twenty-one patients (66%) experienced a treatment-related adverse event (TRAE), with three experiencing grade 3 TRAEs and one experiencing a grade 4 TRAE (per CTCAE v4.0). No grade 5 TRAEs were reported. Objective responses by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) occurred in 22% of patients, with a median duration of response of 7.4 months (range 2.8-45.8 months). Median progression-free survival was 2.6 months (range 0.5-48.4 months), and median overall survival was 6.0 months (range 0.5-51.6+ months). Responses showed no association with HPV status or PD-L1 expression level.
In this heavily pre-treated advanced HNC cohort, atezolizumab had a tolerable safety profile and encouraging activity, with responses observed regardless of HPV status and PD-L1 expression level. These findings warrant further investigation of atezolizumab in HNC. ClinicalTrials.gov number: NCT01375842.
头颈部癌症（HNC）在晚期预后较差。鉴于 HNC 中免疫抑制的肿瘤微环境，抑制程序性死亡配体 1/程序性死亡-1（PD-L1/PD-1）信号通路代表了一种有前途的治疗方法。阿特珠单抗（抗 PD-L1）对许多肿瘤类型有效。在这里，我们报告了 HNC 队列的临床安全性和活性，这是一项 Ia 期 PCD4989g 临床试验。
先前接受过治疗的晚期 HNC 患者接受静脉注射阿特珠单抗，每 3 周一次，共 16 个周期，最长 1 年或直至失去临床获益。患者接受安全性和耐受性监测，并每 6 周评估一次反应。评估了基线 PD-L1 表达水平和人乳头瘤病毒（HPV）状态。
共纳入 32 例患者；7 例（22%）患者的原发性肿瘤位于口腔，18 例（56%）位于口咽，1 例（3%）位于下咽，2 例（6%）位于喉，4 例（13%）位于鼻咽。17 例（53%）患者有≥2 种既往治疗线。21 例（66%）患者发生治疗相关不良事件（TRAE），其中 3 例发生 3 级 TRAE，1 例发生 4 级 TRAE（按 CTCAE v4.0 标准）。无 5 级 TRAE 报告。根据实体瘤反应评价标准 1.1 版（RECIST v1.1），22%的患者出现客观缓解，缓解持续时间中位数为 7.4 个月（范围为 2.8-45.8 个月）。中位无进展生存期为 2.6 个月（范围为 0.5-48.4 个月），中位总生存期为 6.0 个月（范围为 0.5-51.6+ 个月）。反应与 HPV 状态或 PD-L1 表达水平无关。
在这一晚期 HNC 患者中，阿特珠单抗具有可耐受的安全性和令人鼓舞的疗效，无论 HPV 状态和 PD-L1 表达水平如何，均可观察到反应。这些发现证明了阿特珠单抗在 HNC 中的进一步研究是合理的。临床试验注册号：NCT01375842。
