Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Cancer Immunol Immunother. 2024 Aug 6;73(10):199. doi: 10.1007/s00262-024-03784-5.
Patients with recurrent or metastatic head and neck cancers (R/M HNCs) are prone to developing resistance after immunotherapy. This retrospective real-world study aims to investigate whether the addition of anlotinib can reverse resistance to PD-1 inhibitors (PD-1i) and evaluate the efficacy and safety of this combination in R/M HNCs. Main outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Potential biomarkers included PD-L1 expression, lipid index, and genomic profiling. Twenty-one patients with R/M HNCs were included, including 11 nasopharyngeal carcinoma (NPC), five head and neck squamous cell carcinoma (HNSCC), three salivary gland cancers (SGC), and two nasal cavity or paranasal sinus cancers (NC/PNC). Among all patients, ORR was 47.6% (95% CI: 28.6-66.7), with 2 (9.5%) complete response; DCR was 100%. At the median follow-up of 17.1 months, the median PFS and OS were 14.3 months (95% CI: 5.9-NR) and 16.7 months (95% CI:8.4-NR), respectively. The median DOR was 11.2 months (95% CI: 10.1-NR). As per different diseases, the ORR was 45.5% for NPC, 60.0% for HNSCC, 66.7% for SGC, and 50.0% for NC/PNC. Most treatment-related adverse events (TRAEs) were grade 1 or 2 (88.9%). The most common grades 3-4 TRAE was hypertension (28.6%), and two treatment-related deaths occurred due to bleeding. Therefore, adding anlotinib to the original PD-1i could reverse PD-1 blockade resistance, with a favorable response rate, prolonged survival, and acceptable toxicity, indicating the potential as a second-line and subsequent therapy choice in R/M HNCs.
患有复发性或转移性头颈部癌症（R/M HNCs）的患者在接受免疫治疗后容易产生耐药性。本回顾性真实世界研究旨在探讨安罗替尼能否逆转 PD-1 抑制剂（PD-1i）的耐药性，并评估该联合疗法在 R/M HNCs 中的疗效和安全性。主要结局包括客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DOR）和安全性。潜在的生物标志物包括 PD-L1 表达、脂质指数和基因组分析。共纳入 21 例 R/M HNCs 患者，包括 11 例鼻咽癌（NPC）、5 例头颈部鳞状细胞癌（HNSCC）、3 例唾液腺癌（SGC）和 2 例鼻腔或鼻窦癌（NC/PNC）。所有患者的 ORR 为 47.6%（95%CI：28.6-66.7），完全缓解率为 9.5%；DCR 为 100%。在中位随访 17.1 个月时，中位 PFS 和 OS 分别为 14.3 个月（95%CI：5.9-NR）和 16.7 个月（95%CI：8.4-NR），中位 DOR 为 11.2 个月（95%CI：10.1-NR）。按不同疾病类型分析，NPC 的 ORR 为 45.5%，HNSCC 为 60.0%，SGC 为 66.7%，NC/PNC 为 50.0%。大多数治疗相关不良事件（TRAEs）为 1 级或 2 级（88.9%）。最常见的 3-4 级 TRAE 是高血压（28.6%），有 2 例 TRAE 相关死亡是由于出血引起的。因此，在原有的 PD-1i 治疗基础上加用安罗替尼可以逆转 PD-1 阻断耐药，具有较高的缓解率、延长的生存期和可接受的毒性，提示其有可能成为 R/M HNCs 的二线和后续治疗选择。
