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

Abstract

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.

Conflict of interest statement

Conflicts of Interest Statement:

Funding for this study was provided by Bristol Myers Squibb awarded to Drs. Wise-Draper and Haque. PD-L1 staining and TMB analysis was provided by Caris Life Sciences. The authors have no additional relevant conflicts of interest to disclose. Julie McGrath and Michael Korn are employees of Caris Life Science.

©2022 American Association for Cancer Research.

Figures

Figure 1.. Survival Outcomes for Recurrent HNSCC Patients after Salvage Surgery

Kaplan-Meier curves showing disease-free survival (A) and overall survival (B) of the study group and historical controls measured in months from the date of salvage surgery to disease recurrence (A) or last known day alive (B). Subjects were censored at their last known medical contact. * Indicates statistical significance.

Figure 2.. Survival Outcomes by Pathologic Risk and P16 Status

Kaplan-Meier curves showing disease-free survival (A) and overall survival (B) of the study group measured in months from the start of nivolumab therapy stratified by Pathologic Risk. (C and D) Disease free survival and overall survival of the study group stratified by P16 status.

Figure 3:. Disease-free Survival of the Study Group Stratified by PD-L1 Status and Tumor Mutational Burden.

Kaplan-Meier curves showing disease-free survival of the study group measured in months from the start of nivolumab therapy and stratified by PD-L1 expression (A) PD-L1 zero vs PD-L1 ≥1 (B) PD-L1 ≥10 vs all others. (C) disease-free survival and (D) overall survival of the study group stratified by tumor mutational burden ≥10 vs all others.