Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio.
University of Cincinnati Cancer Center, Cincinnati, Ohio.
Clin Cancer Res. 2022 Aug 15;28(16):3464-3472. doi: 10.1158/1078-0432.CCR-21-4554.
Locoregional relapse in patients with head and neck squamous cell carcinoma (HNSCC) is common, approaching 50% for some subsites despite multimodality therapy. Salvage surgery is the standard of care, but able to achieve durable control in only a minority of patients. While adjuvant radiotherapy or chemo-radiotherapy is offered to select patients, this approach can be prohibitively toxic. Given the activity and tolerability of programmed death-1 inhibitors in metastatic HNSCC, we investigated the safety and efficacy of adjuvant nivolumab after salvage surgical resection.
This was an open-label, multi-institutional phase II clinical trial (NCT03355560). Patients with recurrent, resectable HNSCC were enrolled within 6 weeks of salvage surgery. Six 28-day cycles of adjuvant nivolumab were planned. The primary endpoint was 2-year disease-free survival (DFS) more than 58%, based on an institutional historical control group of 71 patients with recurrent HNSCC who underwent salvage surgery.
Between February 2018 and February 2020, 39 patients were enrolled. At a median follow-up of 22.1 months, 2-year DFS was 71.4% [95% confidence interval (CI), 57.8-88.1] and the 2-year overall survival (OS) was 73% (95% CI, 58-91.8). Three of 39 (8%) patients experienced grade 3 treatment-related adverse events and 3 of 39 (8%) discontinued treatment due to side effects. Ten of 39 had locoregional recurrence, while 2 of 10 also had synchronous metastatic disease. There was no difference in DFS between PD ligand-1 (PD-L1)-positive and PD-L1-negative patients. There was a nonsignificant trend toward improved DFS in patients with high tumor mutational burden (P = 0.083).
Adjuvant nivolumab after salvage surgery in locally recurrent HNSCC is well tolerated and showed improved DFS compared with historical controls.
尽管采用了多模式治疗，但头颈部鳞状细胞癌（HNSCC）患者的局部区域复发仍很常见，某些部位的复发率接近 50%。挽救性手术是标准治疗方法，但只能使少数患者获得持久控制。虽然选择合适的患者提供辅助放疗或放化疗，但这种方法可能毒性太大。鉴于程序性死亡-1 抑制剂在转移性 HNSCC 中的活性和耐受性，我们研究了挽救性手术后辅助纳武利尤单抗的安全性和有效性。
这是一项开放标签、多机构的 II 期临床试验（NCT03355560）。在挽救性手术后 6 周内招募了复发性可切除 HNSCC 患者。计划进行 6 个 28 天周期的辅助纳武利尤单抗治疗。主要终点是 2 年无病生存率（DFS）超过 58%，基于 71 例复发性 HNSCC 患者接受挽救性手术后的机构历史对照。
2018 年 2 月至 2020 年 2 月期间，共纳入 39 例患者。中位随访 22.1 个月时，2 年 DFS 为 71.4%（95%CI，57.8-88.1），2 年总生存率（OS）为 73%（95%CI，58-91.8）。39 例患者中有 3 例（8%）出现 3 级治疗相关不良事件，3 例（8%）因副作用停药。39 例中有 10 例发生局部区域复发，其中 10 例中有 2 例也发生同步转移性疾病。PD 配体-1（PD-L1）阳性和 PD-L1 阴性患者的 DFS 无差异。高肿瘤突变负担患者的 DFS 有改善趋势，但无统计学意义（P=0.083）。
复发性 HNSCC 患者在挽救性手术后辅助使用纳武利尤单抗耐受性良好，与历史对照相比，DFS 得到改善。
