Clinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalation

Cancer Immunol Immunother. 2025 Jul 5;74(8):260. doi: 10.1007/s00262-025-04115-y.

Abstract

Background: Non-melanoma skin cancers (NMSC) are the most common malignancies worldwide. While early-stage lesions can be definitively treated with local therapies, advanced stage cutaneous squamous cell carcinoma (cSCC) often requires systemic treatments such as PD-1 inhibitors. These treatments may be administered for prolonged durations; this practice may lead to an unnecessary physical and financial toxicity. The purpose of this study was to evaluate the patterns of disease progression after anti-PD-1 therapy discontinuation in this group of patients.

Methods: This retrospective cohort study included patients diagnosed with advanced cSCC and treated with either cemiplimab or pembrolizumab from 2019 to 2024 at a single university-affiliated tertiary medical center.

Results: The cohort included 131 patients, with a 73% overall response rate. Among the 86 patients with either partial or complete response as the best response included in the final analysis, 40 (47%) patients had a treatment break for at least 3 months, and 46 (53%) continued without discontinuation to a maximal duration of 2 years. After a median follow-up of 29.9 months, 24 (60%) patients in the break group remained progression-free, systemic treatment-free, and alive throughout the follow-up. Four patients (10%) experienced disease progression. Among these, the best overall response was PR in three patients and CR in one patient. Nine (22.5%) patients died due to non-oncological reasons, two (5%) patients died from an unknown cause, and one (2.5%) due to treatment toxicity. The percentage of patients achieving CR was statistically significantly higher in the break group compared to the no-break group.

Conclusions: Our findings advocate for a more tailored approach to the duration of PD-1 inhibitor therapy in cSCC, potentially reducing burdens of overtreatment. Future studies regarding establishing robust predictors for safe treatment discontinuation are required to enhance decision-making in clinical practice.

Keywords: Anti-PD-1 therapy discontinuation; Cutaneous squamous cell carcinoma; PD-1 inhibitors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / immunology
  • Carcinoma, Squamous Cell* / mortality
  • Carcinoma, Squamous Cell* / pathology
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / administration & dosage
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Retrospective Studies
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / immunology
  • Skin Neoplasms* / mortality
  • Skin Neoplasms* / pathology
  • Treatment Outcome
  • Withholding Treatment*

Substances

  • Programmed Cell Death 1 Receptor
  • Immune Checkpoint Inhibitors
  • pembrolizumab
  • Antibodies, Monoclonal, Humanized
  • PDCD1 protein, human
  • cemiplimab