Phase II Trial of Adjuvant Nivolumab Following Salvage Resection in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck

Clin Cancer Res. 2022 Aug 15;28(16):3464-3472. doi: 10.1158/1078-0432.CCR-21-4554.


Purpose: 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.

Patients and methods: 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.

Results: 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).

Conclusions: Adjuvant nivolumab after salvage surgery in locally recurrent HNSCC is well tolerated and showed improved DFS compared with historical controls.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • B7-H1 Antigen
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / surgery
  • Head and Neck Neoplasms* / drug therapy
  • Humans
  • Neoplasm Recurrence, Local / pathology
  • Nivolumab / adverse effects
  • Squamous Cell Carcinoma of Head and Neck / therapy


  • B7-H1 Antigen
  • Nivolumab

Associated data