Chen Jia-Ying, Huang Nai-Si, Wei Wen-Jun, Hu Jia-Qian, Cao Yi-Ming, Shen Qiang, Lu Zhong-Wu, Wang Yu-Long, Wang Yu, Ji Qing-Hai
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Centre, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Ann Surg Oncol. 2023 Nov;30(12):7172-7180. doi: 10.1245/s10434-023-14031-z. Epub 2023 Aug 5.
Surgery is the primary treatment for locally advanced differentiated thyroid cancer (DTC). However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced DTC. Surufatinib targets multiple kinases, which is efficient, tolerable, and safe in patients with radioiodine-refractory DTC. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity in advanced solid tumors. This study was designed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced DTC in the neoadjuvant setting.
In this single-arm, phase II study, patients with pathologically confirmed unresectable or borderline resectable DTC were eligible and received a combination of 250 mg of surufatinib (orally daily) with 240 mg of toripalimab (intravenous, every 3 weeks). Treatment continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity, or investigator decision. Primary endpoint was objective response rate (ORR). Secondary endpoints included R0/1 resection rate, adverse events (AEs), etc. RESULTS: Ten patients were enrolled and received at least 4 cycles of treatment. The ORR was 60%. Nine patients received R0/1 resections after neoadjuvant treatment. The median best percentage change in the sum of the target lesion diameter was 32%. Most adverse events (AEs) were grade 1 or 2.
Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced DTC was feasible, and the majority of patients achieved R0/1 resection. It represents a new option for locally advanced DTC and needs further investigation.
手术是局部晚期分化型甲状腺癌（DTC）的主要治疗方法。然而，一些局部晚期患者不适合进行R0/1切除。局部晚期DTC新辅助治疗的证据有限。苏呋替尼靶向多种激酶，在放射性碘难治性DTC患者中有效、耐受性良好且安全。此外，苏呋替尼联合托瑞帕利单抗（一种抗PD-1抗体）在晚期实体瘤中显示出令人鼓舞的抗肿瘤活性。本研究旨在评估苏呋替尼联合托瑞帕利单抗在新辅助治疗局部晚期DTC中的疗效和安全性。
在这项单臂II期研究中，病理确诊为不可切除或临界可切除DTC的患者符合条件，接受250mg苏呋替尼（每日口服）与240mg托瑞帕利单抗（静脉注射，每3周一次）的联合治疗。治疗持续至满足根治性手术条件、疾病进展、撤回同意、出现不可接受的毒性或研究者决定终止。主要终点是客观缓解率（ORR）。次要终点包括R0/1切除率、不良事件（AE）等。结果：10名患者入组并接受了至少4个周期的治疗。ORR为60%。9名患者在新辅助治疗后接受了R0/1切除。目标病灶直径总和的最佳百分比变化中位数为32%。大多数不良事件为1级或2级。
苏呋替尼联合托瑞帕利单抗作为局部晚期DTC的新辅助治疗是可行的，大多数患者实现了R0/1切除。它代表了局部晚期DTC的一种新选择，需要进一步研究。
