# Progression-Free Survival and Treatment-Free Interval in Head and Neck Cancer with Long-Term Response to Nivolumab: Timing of Active Discontinuation

## TL;DR

The study finds that for some head and neck cancer patients, stopping nivolumab treatment after 3 years may be optimal as survival rates stabilize.

## Contribution

The study identifies a 3-year plateau in progression-free survival for long-term responders to nivolumab in head and neck cancer.

## Key findings

- Progression-free survival leveled off after 3 years in patients with head and neck cancer.
- Patients discontinued treatment after 3 years had a median treatment-free interval of 15.1 months.
- The optimal timing for active discontinuation of nivolumab is suggested to be at 3 years.

## Abstract

This retrospective study aimed to determine the optimal timing of active discontinuation of long-term responders to immune checkpoint inhibitors in patients with recurrent/metastatic head and neck squamous cell carcinoma. We analyzed treatment duration and treatment-free interval (TFI) in 227 nivolumab-treated patients and determined the timing when progression-free survival (PFS) leveled off and when patients discontinued for unplanned reasons (toxicity or patient decision). The 3-year and 6-year PFS was 15.9% and 15.3%, respectively. The PFS curve was completely flat at 3 years. The median time for patients to request discontinuation was 36.8 months, with a median TFI of 15.1 months. The median time for discontinuation due to toxicity was 18.9 months, with a median TFI of 30.6 months. Given that the PFS curve completely leveled off at 3 years and the median time of discontinuation at the patient’s choice was 3 years, we suggest considering treatment completion at 3 years.

The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range 0.03–81.9): Ongoing group, 41.8 (5.6–81.9); Decision group, 36.8 (4.0–70.1); Toxicity group, 30.6 (2.8–64.8); and progressive disease group, 2.0 (0.03–42.9). TFI in the Decision group was 15.1 months (0.6–61.6) and 30.6 months (2.8–64.8) in the Toxicity group. Long-term responses in R/M HNSCC patients treated with nivolumab are rare but gradually increasing. For this patient group, our best estimate of the optimal time to end treatment is 3 years, as the PFS in this study reached a plateau at that timepoint.